Generic placeholder image

Protein & Peptide Letters


ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Review Article

Renin-Angiotensin System and Alzheimer’s Disease Pathophysiology: From the Potential Interactions to Therapeutic Perspectives

Author(s): Victor Teatini Ribeiro *, Leonardo Cruz de Souza and Ana Cristina Simões e Silva

Volume 27, Issue 6, 2020

Page: [484 - 511] Pages: 28

DOI: 10.2174/0929866527666191230103739

Price: $65


New roles of the Renin-Angiotensin System (RAS), apart from fluid homeostasis and Blood Pressure (BP) regulation, are being progressively unveiled, since the discoveries of RAS alternative axes and local RAS in different tissues, including the brain. Brain RAS is reported to interact with pathophysiological mechanisms of many neurological and psychiatric diseases, including Alzheimer’s Disease (AD). Even though AD is the most common cause of dementia worldwide, its pathophysiology is far from elucidated. Currently, no treatment can halt the disease course. Successive failures of amyloid-targeting drugs have challenged the amyloid hypothesis and increased the interest in the inflammatory and vascular aspects of AD. RAS compounds, both centrally and peripherally, potentially interact with neuroinflammation and cerebrovascular regulation. This narrative review discusses the AD pathophysiology and its possible interaction with RAS, looking forward to potential therapeutic approaches. RAS molecules affect BP, cerebral blood flow, neuroinflammation, and oxidative stress. Angiotensin (Ang) II, via angiotensin type 1 receptors may promote brain tissue damage, while Ang-(1-7) seems to elicit neuroprotection. Several studies dosed RAS molecules in AD patients' biological material, with heterogeneous results. The link between AD and clinical conditions related to classical RAS axis overactivation (hypertension, heart failure, and chronic kidney disease) supports the hypothesized role of this system in AD. Additionally, RAStargeting drugs as Angiotensin Converting Enzyme inhibitors (ACEis) and Angiotensin Receptor Blockers (ARBs) seem to exert beneficial effects on AD. Results of randomized controlled trials testing ACEi or ARBs in AD are awaited to elucidate whether AD-RAS interaction has implications on AD therapeutics.

Keywords: Renin-angiotensin system, Alzheimer’s disease, angiotensin II, angiotensin-(1-7), dementia, neuroinflammation, amyloid hypothesis.

Graphical Abstract
Patel, S.; Rauf, A.; Khan, H.; Abu-Izneid, T. Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies. Biomed. Pharmacother., 2017, 94, 317-325.
[] [PMID: 28772209]
Rocha, N.P.; Simoes E Silva, A.C.; Prestes, T.R.R.; Feracin, V.; Machado, C.A.; Ferreira, R.N.; Teixeira, A.L.; de Miranda, A.S. RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders. Curr. Med. Chem., 2018, 25(28), 3333-3352.
[] [PMID: 29484978]
Kehoe, P.G.; Wilcock, G.K. Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer’s disease? Lancet Neurol., 2007, 6(4), 373-378.
[] [PMID: 17362841]
Hajjar, I.; Rodgers, K. Do angiotensin receptor blockers prevent Alzheimer’s disease? Curr. Opin. Cardiol., 2013, 28(4), 417-425.
[] [PMID: 23703253]
Hilal-Dandan, R. Renin and Angiotensin. InGoodman & Gilman’s The Pharmacological Bases of Therapeutics; Brunton, L.L.; Hilal-Dandan, R.; Knollmann, B.C., Eds.; McGraw-Hill Education: New York, NY, 2018, pp. 471-489.
Sparks, M.A.; Crowley, S.D.; Gurley, S.B.; Mirotsou, M.; Coffman, T.M. Classical Renin-Angiotensin system in kidney physiology. Compr. Physiol., 2014, 4(3), 1201-1228.
[] [PMID: 24944035]
Paul, M.; Poyan Mehr, A.; Kreutz, R. Physiology of local renin-angiotensin systems. Physiol. Rev., 2006, 86(3), 747-803.
[] [PMID: 16816138]
Corvol, P.; Michaud, A.; Soubrier, F.; Williams, T.A. Recent advances in knowledge of the structure and function of the angiotensin I converting enzyme. J. Hypertens. Suppl., 1995, 13(3), S3-S10.
[] [PMID: 8592248]
Carey, R.M. Update on angiotensin AT2 receptors. Curr. Opin. Nephrol. Hypertens., 2017, 26(2), 91-96.
[] [PMID: 27906747]
Sjöström, H.; Norén, O.; Olsen, J. Structure and Function of Aminopeptidase N. In: Cellular Peptidases in Immune Functions and Diseases. 2nd Ed, 2011, Vol. 82, 25-34.
Goto, Y.; Hattori, A.; Ishii, Y.; Mizutani, S.; Tsujimoto, M. Enzymatic properties of human aminopeptidase A. Regulation of its enzymatic activity by calcium and angiotensin IV. J. Biol. Chem., 2006, 281(33), 23503-23513.
[] [PMID: 16790432]
Donoghue, M.; Hsieh, F.; Baronas, E.; Godbout, K.; Gosselin, M.; Stagliano, N.; Donovan, M.; Woolf, B.; Robison, K.; Jeyaseelan, R.; Breitbart, R.E.; Acton, S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res., 2000, 87(5), E1-E9.
[] [PMID: 10969042]
Tipnis, S.R.; Hooper, N.M.; Hyde, R.; Karran, E.; Christie, G.; Turner, A.J. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem., 2000, 275(43), 33238-33243.
[] [PMID: 10924499]
Santos, R.A.S.; Ferreira, A.J.; Verano-Braga, T.; Bader, M. Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: new players of the renin-angiotensin system. J. Endocrinol., 2013, 216(2), R1-R17.
[] [PMID: 23092879]
Almeida-Santos, A.F.; Kangussu, L.M.; Campagnole-Santos, M.J. The renin-angiotensin system and the neurodegenerative diseases: A brief review. Protein Pept. Lett., 2017, 24(9), 841-853.
[] [PMID: 28828974]
Santos, R.A.S.; Simoes e Silva, A.C.; Maric, C.; Silva, D.M.R.; Machado, R.P.; de Buhr, I.; Heringer-Walther, S.; Pinheiro, S.V.B.; Lopes, M.T.; Bader, M.; Mendes, E.P.; Lemos, V.S.; Campagnole-Santos, M.J.; Schultheiss, H.P.; Speth, R.; Walther, T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8258-8263.
[] [PMID: 12829792]
Santos, R.A. Angiotensin-(1-7). Hypertension, 2014, 63(6), 1138-1147.
[] [PMID: 24664288]
Turner, A.J. Chapter 25 - ACE2 Cell Biology, Regulation, and Physiological Functions. In: The Protective Arm of the Renin Angiotensin System (RAS). Unger. T.; Steckelings, U.M.; dos Santos, R.A.S., Eds.; Academic Press: Boston, 2015; pp. 185-89
Iadecola, C. The neurovascular unit coming of age: A journey through neurovascular coupling in health and disease. Neuron, 2017, 96(1), 17-42.
[] [PMID: 28957666]
Armstead, W.M. Cerebral blood flow autoregulation and dysautoregulation. Anesthesiol. Clin., 2016, 34(3), 465-477.
[] [PMID: 27521192]
Novak, V.; Hajjar, I. The relationship between blood pressure and cognitive function. Nat. Rev. Cardiol., 2010, 7(12), 686-698.
[] [PMID: 20978471]
Mogi, M.; Iwanami, J.; Horiuchi, M. Roles of brain angiotensin II in cognitive function and dementia. Int. J. Hypertens., 2012, 2012169649
[] [PMID: 23304450]
Jackson, L.; Eldahshan, W.; Fagan, S.C.; Ergul, A. Within the brain: The renin angiotensin system. Int. J. Mol. Sci., 2018, 19(3), 876.
[] [PMID: 29543776]
van Thiel, B.S.; Góes Martini, A.; Te Riet, L.; Severs, D.; Uijl, E.; Garrelds, I.M.; Leijten, F.P.J.; van der Pluijm, I.; Essers, J.; Qadri, F.; Alenina, N.; Bader, M.; Paulis, L.; Rajkovicova, R.; Domenig, O.; Poglitsch, M.; Danser, A.H.J. Brain renin-angiotensin system: Does it exist? Hypertension, 2017, 69(6), 1136-1144.
[] [PMID: 28396529]
Zühlke, L.; Engel, M.E.; Karthikeyan, G.; Rangarajan, S.; Mackie, P.; Cupido, B.; Mauff, K.; Islam, S.; Joachim, A.; Daniels, R.; Francis, V.; Ogendo, S.; Gitura, B.; Mondo, C.; Okello, E.; Lwabi, P.; Al-Kebsi, M.M.; Hugo-Hamman, C.; Sheta, S.S.; Haileamlak, A.; Daniel, W.; Goshu, D.Y.; Abdissa, S.G.; Desta, A.G.; Shasho, B.A.; Begna, D.M.; ElSayed, A.; Ibrahim, A.S.; Musuku, J.; Bode-Thomas, F.; Okeahialam, B.N.; Ige, O.; Sutton, C.; Misra, R.; Abul Fadl, A.; Kennedy, N.; Damasceno, A.; Sani, M.; Ogah, O.S.; Olunuga, T.; Elhassan, H.H.; Mocumbi, A.O.; Adeoye, A.M.; Mntla, P.; Ojji, D.; Mucumbitsi, J.; Teo, K.; Yusuf, S.; Mayosi, B.M. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur. Heart J., 2015, 36(18), 1115-22a.
[] [PMID: 25425448]
Ren, L.; Lu, X.; Danser, A.H.J. Revisiting the brain renin-angiotensin system-focus on novel therapies. Curr. Hypertens. Rep., 2019, 21(4), 28.
[] [PMID: 30949864]
Uijl, E.; Ren, L.; Danser, A.H.J. Angiotensin generation in the brain: a re-evaluation. Clin. Sci. (Lond.), 2018, 132(8), 839-850.
[] [PMID: 29712882]
Sisó, S.; Jeffrey, M.; González, L. Sensory circumventricular organs in health and disease. Acta Neuropathol., 2010, 120(6), 689-705.
[] [PMID: 20830478]
Hammer, A.; Stegbauer, J.; Linker, R.A. Macrophages in neuroinflammation: role of the renin-angiotensin-system. Pflugers Arch., 2017, 469(3-4), 431-444.
[] [PMID: 28190090]
Tota, S.; Goel, R.; Pachauri, S.D.; Rajasekar, N.; Najmi, A.K.; Hanif, K.; Nath, C. Effect of angiotensin II on spatial memory, cerebral blood flow, cholinergic neurotransmission, and brain derived neurotrophic factor in rats. Psychopharmacology (Berl.), 2013, 226(2), 357-369.
[] [PMID: 23192311]
McCarthy, C.A.; Widdop, R.E.; Deliyanti, D.; Wilkinson-Berka, J.L. Brain and retinal microglia in health and disease: an unrecognized target of the renin-angiotensin system. Clin. Exp. Pharmacol. Physiol., 2013, 40(8), 571-579.
[] [PMID: 23601050]
Labandeira-Garcia, J.L.; Rodríguez-Perez, A.I.; Garrido-Gil, P.; Rodriguez-Pallares, J.; Lanciego, J.L.; Guerra, M.J. Brain renin-angiotensin system and microglial polarization: Implications for aging and neurodegeneration. Front. Aging Neurosci., 2017, 9(MAY), 129.
[] [PMID: 28515690]
Biancardi, V.C.; Stranahan, A.M.; Krause, E.G.; de Kloet, A.D.; Stern, J.E. Cross talk between AT1 receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus. Am. J. Physiol. Heart Circ. Physiol., 2016, 310(3), H404-H415.
[] [PMID: 26637556]
Banks, W.A. The blood-brain barrier as an endocrine tissue. Nat. Rev. Endocrinol., 2019, 15(8), 444-455.
[] [PMID: 31127254]
Farag, E.; Sessler, D.I.; Ebrahim, Z.; Kurz, A.; Morgan, J.; Ahuja, S.; Maheshwari, K.; John Doyle, D. The renin angiotensin system and the brain: New developments. J. Clin. Neurosci., 2017, 46, 1-8.
[] [PMID: 28890045]
Capone, C.; Faraco, G.; Park, L.; Cao, X.; Davisson, R.L.; Iadecola, C. The cerebrovascular dysfunction induced by slow pressor doses of angiotensin II precedes the development of hypertension. Am. J. Physiol. Heart Circ. Physiol., 2011, 300(1), H397-H407.
[] [PMID: 20971763]
Inaba, S.; Iwai, M.; Furuno, M.; Tomono, Y.; Kanno, H.; Senba, I.; Okayama, H.; Mogi, M.; Higaki, J.; Horiuchi, M. Continuous activation of renin-angiotensin system impairs cognitive function in renin/angiotensinogen transgenic mice. Hypertension, 2009, 53(2), 356-362.
[] [PMID: 19047580]
Sen, S.; Gürel, N.; Ufuktepe, B.; Özünal, Z.G.; Büyüklü, Ç.; Üresin, Y. Evaluating the relationship of blood pressure, plasma angiotensin peptides and aldosterone with cognitive functions in patients with hypertension. EXCLI J., 2017, 16, 245-255.
[] [PMID: 28507470]
Yasar, S.; Varma, V.R.; Harris, G.C.; Carlson, M.C. Associations of angiotensin converting enzyme-1 and Angiotensin II blood levels and cognitive function. J. Alzheimers Dis., 2018, 63(2), 655-664.
[] [PMID: 29660936]
Wright, J.W.; Harding, J.W. Brain renin-angiotensin--a new look at an old system. Prog. Neurobiol., 2011, 95(1), 49-67.
[] [PMID: 21777652]
de Kloet, A.D.; Steckelings, U.M.; Sumners, C. Protective angiotensin type 2 receptors in the brain and hypertension. Curr. Hypertens. Rep., 2017, 19(6), 46.
[] [PMID: 28488048]
Kerr, D.S.; Bevilaqua, L.R.M.; Bonini, J.S.; Rossato, J.I.; Köhler, C.A.; Medina, J.H.; Izquierdo, I.; Cammarota, M. Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism. Psychopharmacology (Berl.), 2005, 179(3), 529-535.
[] [PMID: 15551065]
Jing, F.; Mogi, M.; Sakata, A.; Iwanami, J.; Tsukuda, K.; Ohshima, K.; Min, L.J.; Steckelings, U.M.; Unger, T.; Dahlöf, B.; Horiuchi, M. Direct stimulation of angiotensin II type 2 receptor enhances spatial memory. J. Cereb. Blood Flow Metab., 2012, 32(2), 248-255.
[] [PMID: 21971355]
Chappell, M.C.; Brosnihan, K.B.; Diz, D.I.; Ferrario, C.M. Identification of angiotensin-(1-7) in rat brain. Evidence for differential processing of angiotensin peptides. J. Biol. Chem., 1989, 264(28), 16518-16523.
[PMID: 2777795]
Pereira, M.G.A.G.; Souza, L.L.; Becari, C.; Duarte, D.A.; Camacho, F.R.B.; Oliveira, J.A.C.; Gomes, M.D.; Oliveira, E.B.; Salgado, M.C.O.; Garcia-Cairasco, N.; Costa-Neto, C.M. Angiotensin II-independent angiotensin-(1-7) formation in rat hippocampus: involvement of thimet oligopeptidase. Hypertension, 2013, 62(5), 879-885.
[] [PMID: 24041943]
Becker, L.K.; Etelvino, G.M.; Walther, T.; Santos, R.A.S.; Campagnole-Santos, M.J. Immunofluorescence localization of the receptor Mas in cardiovascular-related areas of the rat brain. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(3), H1416-H1424.
[] [PMID: 17496218]
Freund, M.; Walther, T.; von Bohlen und Halbach, O. Immunohistochemical localization of the angiotensin-(1-7) receptor Mas in the murine forebrain. Cell Tissue Res., 2012, 348(1), 29-35.
[] [PMID: 22362508]
Zhang, Y.; Lu, J.; Shi, J.; Lin, X.; Dong, J.; Zhang, S.; Liu, Y.; Tong, Q. Central administration of angiotensin-(1-7) stimulates nitric oxide release and upregulates the endothelial nitric oxide synthase expression following focal cerebral ischemia/reperfusion in rats. Neuropeptides, 2008, 42(5-6), 593-600.
[] [PMID: 18990443]
Lu, J.; Zhang, Y.; Shi, J. Effects of intracerebroventricular infusion of angiotensin-(1-7) on bradykinin formation and the kinin receptor expression after focal cerebral ischemia-reperfusion in rats. Brain Res., 2008, 1219, 127-135.
[] [PMID: 18538311]
Wu, J.; Zhao, D.; Wu, S.; Wang, D. Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9. Eur. J. Pharmacol., 2015, 748, 30-36.
[] [PMID: 25523481]
Ho, J.K.; Nation, D.A. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. Neurosci. Biobehav. Rev., 2018, 92, 209-225.
dos Santos, R.A.S.; Sampaio, W.O. Mas Receptor: Vascular and blood pressure effects. In: The Protective Arm of System the Renin-Angiotensin Functional Aspects and Therapeutic Implications; Academic Press: Cambridge, USA, 2015, pp. 197-199.
von Bohlen und Halbach, O. Angiotensin IV in the central nervous system. Cell Tissue Res., 2003, 311(1), 1-9.
[] [PMID: 12483279]
Chai, S.Y.; Bastias, M.A.; Clune, E.F.; Matsacos, D.J.; Mustafa, T.; Lee, J.H.; McDowall, S.G.; Paxinos, G.; Mendelsohn, F.A.; Albiston, A.L. Distribution of angiotensin IV binding sites (AT4 receptor) in the human forebrain, midbrain and pons as visualised by in vitro receptor autoradiography. J. Chem. Neuroanat., 2000, 20(3-4), 339-348.
[] [PMID: 11207430]
Lee, J.; Chai, S.Y.; Mendelsohn, F.A.O.; Morris, M.J.; Allen, A.M. Potentiation of cholinergic transmission in the rat hippocampus by angiotensin IV and LVV-hemorphin-7. Neuropharmacology, 2001, 40(4), 618-623.
[] [PMID: 11249971]
Kramár, E.A.; Armstrong, D.L.; Ikeda, S.; Wayner, M.J.; Harding, J.W.; Wright, J.W. The effects of angiotensin IV analogs on long-term potentiation within the CA1 region of the hippocampus in vitro. Brain Res., 2001, 897(1-2), 114-121.
[] [PMID: 11282364]
Wayner, M.J.; Armstrong, D.L.; Phelix, C.F.; Wright, J.W.; Harding, J.W.; Angiotensin, I.V. Angiotensin IV enhances LTP in rat dentate gyrus in vivo. Peptides, 2001, 22(9), 1403-1414.
[] [PMID: 11514021]
Benoist, C.C.; Wright, J.W.; Zhu, M.; Appleyard, S.M.; Wayman, G.A.; Harding, J.W. Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs. J. Pharmacol. Exp. Ther., 2011, 339(1), 35-44.
[] [PMID: 21719467]
Kramár, E.A.; Harding, J.W.; Wright, J.W. Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes. Regul. Pept., 1997, 68(2), 131-138.
[] [PMID: 9110385]
Lane, C.A.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70.
[] [PMID: 28872215]
Morley, J.E.; Farr, S.A.; Nguyen, A.D. Alzheimer Disease. Clin. Geriatr. Med., 2018, 34(4), 591-601.
[] [PMID: 30336989]
Gebre, A.K.; Altaye, B.M.; Atey, T.M.; Tuem, K.B.; Berhe, D.F. Targeting renin-angiotensin system against Alzheimer’s disease. Front. Pharmacol., 2018, 9, 440.
[] [PMID: 29760662]
Dubois, B.; Feldman, H.H.; Jacova, C.; Cummings, J.L.; Dekosky, S.T.; Barberger-Gateau, P.; Delacourte, A.; Frisoni, G.; Fox, N.C.; Galasko, D.; Gauthier, S.; Hampel, H.; Jicha, G.A.; Meguro, K.; O’Brien, J.; Pasquier, F.; Robert, P.; Rossor, M.; Salloway, S.; Sarazin, M.; de Souza, L.C.; Stern, Y.; Visser, P.J.; Scheltens, P. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol., 2010, 9(11), 1118-1127.
[] [PMID: 20934914]
Scheltens, P.; Blennow, K.; Breteler, M.M.B.; de Strooper, B.; Frisoni, G.B.; Salloway, S.; Van der Flier, W.M. Alzheimer’s disease. Lancet, 2016, 388(10043), 505-517.
[] [PMID: 26921134]
Polanco, J.C.; Li, C.; Bodea, L.G.; Martinez-Marmol, R.; Meunier, F.A.; Götz, J. Amyloid-β and tau complexity - towards improved biomarkers and targeted therapies. Nat. Rev. Neurol., 2018, 14(1), 22-39.
[] [PMID: 29242522]
Serrano-Pozo, A.; Frosch, M.P.; Masliah, E.; Hyman, B.T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med., 2011, 1(1), a006189-a006189.
[] [PMID: 22229116]
Thal, D.R.; Rüb, U.; Orantes, M.; Braak, H. Phases of A β-deposition in the human brain and its relevance for the development of AD. Neurology, 2002, 58(12), 1791-1800.
[] [PMID: 12084879]
Braak, H.; Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol., 1991, 82(4), 239-259.
[] [PMID: 1759558]
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s Disease. Neurology, 1984, 34(7), 939-944.
[] [PMID: 6610841]
Sanford, A.M. Mild cognitive impairment. Clin. Geriatr. Med., 2017, 33(3), 325-337.
[] [PMID: 28689566]
Hersi, M.; Irvine, B.; Gupta, P.; Gomes, J.; Birkett, N.; Krewski, D. Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence. Neurotoxicology, 2017, 61, 143-187.
[] [PMID: 28363508]
Lee, J.C.; Kim, S.J.; Hong, S.; Kim, Y. Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers. Exp. Mol. Med., 2019, 51(5), 53.
[] [PMID: 31073121]
Dubois, B.; Feldman, H.H.; Jacova, C.; Hampel, H.; Molinuevo, J.L.; Blennow, K.; DeKosky, S.T.; Gauthier, S.; Selkoe, D.; Bateman, R.; Cappa, S.; Crutch, S.; Engelborghs, S.; Frisoni, G.B.; Fox, N.C.; Galasko, D.; Habert, M.O.; Jicha, G.A.; Nordberg, A.; Pasquier, F.; Rabinovici, G.; Robert, P.; Rowe, C.; Salloway, S.; Sarazin, M.; Epelbaum, S.; de Souza, L.C.; Vellas, B.; Visser, P.J.; Schneider, L.; Stern, Y.; Scheltens, P.; Cummings, J.L. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol., 2014, 13(6), 614-629.
[] [PMID: 24849862]
Jack, C.R., Jr; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Dunn, B.; Haeberlein, S.B.; Holtzman, D.M.; Jagust, W.; Jessen, F.; Karlawish, J.; Liu, E.; Molinuevo, J.L.; Montine, T.; Phelps, C.; Rankin, K.P.; Rowe, C.C.; Scheltens, P.; Siemers, E.; Snyder, H.M.; Sperling, R. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement., 2018, 14(4), 535-562.
[] [PMID: 29653606]
Knopman, D.S.; Petersen, R.C.; Jack, C.R., Jr A brief history of “Alzheimer disease”: Multiple meanings separated by a common name. Neurology, 2019, 92(22), 1053-1059.
[] [PMID: 31028129]
Briggs, R.; Kennelly, S.P.; O’Neill, D. Drug treatments in Alzheimers disease. Clin. Med. (Northfield. Il), 2016, 16(3), 247- 253.
Schliebs, R.; Arendt, T. The cholinergic system in aging and neuronal degeneration. Behav. Brain Res., 2011, 221(2), 555-563.
[] [PMID: 21145918]
Wang, R.; Reddy, P.H. Role of glutamate and NMDA receptors in Alzheimer’s disease. J. Alzheimers Dis., 2017, 57(4), 1041-1048.
[] [PMID: 27662322]
Villemagne, V.L.; Burnham, S.; Bourgeat, P.; Brown, B.; Ellis, K.A.; Salvado, O.; Szoeke, C.; Macaulay, S.L.; Martins, R.; Maruff, P.; Ames, D.; Rowe, C.C.; Masters, C.L. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol., 2013, 12(4), 357-367.
[] [PMID: 23477989]
Querfurth, H.W.; LaFerla, F.M. Alzheimer’s disease. N. Engl. J. Med., 2010, 362(4), 329-344.
[] [PMID: 20107219]
Muckle, L.; Sekloe, D. Neurotoxicity of amyloid β-protein: Synaptic and network. Cold Spring Harb. Perspect. Med., 2014, •••, 1-17.
Ittner, L.M.; Götz, J. Amyloid-β and tau--a toxic pas de deux in Alzheimer’s disease. Nat. Rev. Neurosci., 2011, 12(2), 65-72.
[] [PMID: 21193853]
Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med., 2016, 8(6), 595-608.
[] [PMID: 27025652]
Karran, E.; Mercken, M.; De Strooper, B. The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat. Rev. Drug Discov., 2011, 10(9), 698-712.
[] [PMID: 21852788]
Wang, J.; Gu, B.J.; Masters, C.L.; Wang, Y-J. A systemic view of Alzheimer disease - insights from amyloid-β metabolism beyond the brain. Nat. Rev. Neurol., 2017, 13(10), 612-623.
[] [PMID: 28960209]
Giacobini, E.; Gold, G. Alzheimer disease therapy--moving from amyloid-β to tau. Nat. Rev. Neurol., 2013, 9(12), 677-686.
[] [PMID: 24217510]
Panza, F.; Lozupone, M.; Dibello, V.; Greco, A.; Daniele, A.; Seripa, D.; Logroscino, G.; Imbimbo, B.P. Are antibodies directed against amyloid-β (Aβ) oligomers the last call for the Aβ hypothesis of Alzheimer’s disease? Immunotherapy, 2019, 11(1), 3-6.
[] [PMID: 30702009]
Cummings, J. Lessons learned from Alzheimer disease: Clinical trials with negative outcomes. Clin. Transl. Sci., 2018, 11(2), 147-152.
[] [PMID: 28767185]
Schott, J.M.; Aisen, P.S.; Cummings, J.L.; Howard, R.J.; Fox, N.C. Unsuccessful trials of therapies for Alzheimer’s disease. Lancet, 2019, 393(10166), 29.
[] [PMID: 30614456]
Karran, E.; Hardy, J. A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease. Ann. Neurol., 2014, 76(2), 185-205.
[] [PMID: 24853080]
Anderson, R.M.; Hadjichrysanthou, C.; Evans, S.; Wong, M.M. Why do so many clinical trials of therapies for Alzheimer’s disease fail? Lancet, 2017, 390(10110), 2327-2329.
[] [PMID: 29185425]
Golde, T.E.; Schneider, L.S.; Koo, E.H. Anti-aβ therapeutics in Alzheimer’s disease: the need for a paradigm shift. Neuron, 2011, 69(2), 203-213.
[] [PMID: 21262461]
Selkoe, D.J. Alzheimer disease and aducanumab: adjusting our approach. Nat. Rev. Neurol., 2019, 15(7), 365-366.
[] [PMID: 31138932]
Castello, M.A.; Soriano, S. On the origin of Alzheimer’s disease. Trials and tribulations of the amyloid hypothesis. Ageing Res. Rev., 2014, 13(1), 10-12.
[] [PMID: 24252390]
Transactions, B.S. The amyloid cascade hypothesis has misled the pharmaceutical industry. Biochem. Soc. Trans., 2011, 39(4), 920-923.
[] [PMID: 21787324]
Kepp, K.P. Ten challenges of the amyloid hypothesis of Alzheimer’s disease. J. Alzheimers Dis., 2017, 55(2), 447-457.
[] [PMID: 27662304]
Husain, M. Alzheimer’s disease: time to focus on the brain, not just molecules. Brain, 2017, 140(2), 251-253.
[] [PMID: 28137952]
Zhu, X.; Lee, H.G.; Perry, G.; Smith, M.A. Alzheimer disease, the two-hit hypothesis: an update. Biochim. Biophys. Acta, 2007, 1772(4), 494-502.
[] [PMID: 17142016]
de la Torre, J.C. The vascular hypothesis of Alzheimer’s disease: bench to bedside and beyond. Neurodegener. Dis., 2010, 7(1-3), 116-121.
[] [PMID: 20173340]
Wang, Y.; Mandelkow, E. Tau in physiology and pathology. Nat. Rev. Neurosci., 2016, 17(1), 5-21.
[] [PMID: 26631930]
Ballatore, C.; Lee, V.M.Y.; Trojanowski, J.Q. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat. Rev. Neurosci., 2007, 8(9), 663-672.
[] [PMID: 17684513]
Tapia-Rojas, C.; Cabezas-Opazo, F.; Deaton, C.A.; Vergara, E.H.; Johnson, G.V.W.; Quintanilla, R.A. It’s all about tau. Prog. Neurobiol., 2019, 175, 54-76.
[] [PMID: 30605723]
Heppner, F.L.; Ransohoff, R.M.; Becher, B. Immune attack: the role of inflammation in Alzheimer disease. Nat. Rev. Neurosci., 2015, 16(6), 358-372.
[] [PMID: 25991443]
Heneka, M.T.; Carson, M.J.; El Khoury, J.; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; Herrup, K.; Frautschy, S.A.; Finsen, B.; Brown, G.C.; Verkhratsky, A.; Yamanaka, K.; Koistinaho, J.; Latz, E.; Halle, A.; Petzold, G.C.; Town, T.; Morgan, D.; Shinohara, M.L.; Perry, V.H.; Holmes, C.; Bazan, N.G.; Brooks, D.J.; Hunot, S.; Joseph, B.; Deigendesch, N.; Garaschuk, O.; Boddeke, E.; Dinarello, C.A.; Breitner, J.C.; Cole, G.M.; Golenbock, D.T.; Kummer, M.P. Neuroinflammation in Alzheimer’s disease. Lancet Neurol., 2015, 14(4), 388-405.
[] [PMID: 25792098]
Ransohoff, R.M. How neuroinflammation contributes to neurodegeneration. Science, 2016, 353(6301), 772-77.
Suárez-Calvet, M.; Kleinberger, G.; Araque Caballero, M.Á.; Brendel, M.; Rominger, A.; Alcolea, D.; Fortea, J.; Lleó, A.; Blesa, R.; Gispert, J.D.; Sánchez-Valle, R.; Antonell, A.; Rami, L.; Molinuevo, J.L.; Brosseron, F.; Traschütz, A.; Heneka, M.T.; Struyfs, H.; Engelborghs, S.; Sleegers, K.; Van Broeckhoven, C.; Zetterberg, H.; Nellgård, B.; Blennow, K.; Crispin, A.; Ewers, M.; Haass, C. sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer’s disease and associate with neuronal injury markers. EMBO Mol. Med., 2016, 8(5), 466-476.
[] [PMID: 26941262]
Hansen, D.V.; Hanson, J.E.; Sheng, M. Microglia in Alzheimer’s disease. J. Cell Biol., 2018, 217(2), 459-472.
[] [PMID: 29196460]
López-Valdés, H.E.; Martínez-Coria, H. The role of neuroinflammation in age-related dementias. Rev. Invest. Clin., 2016, 68(1), 40-48.,
[PMID: 27028176]
Subhramanyam, C.S.; Wang, C.; Hu, Q.; Dheen, S.T. Microglia-mediated neuroinflammation in neurodegenerative diseases. Semin. Cell Dev. Biol., 2019, 94, 112-120.
[] [PMID: 31077796]
Lue, L-F.; Kuo, Y-M.; Beach, T.; Walker, D.G. Microglia activation and anti-inflammatory regulation in Alzheimer’s disease. Mol. Neurobiol., 2010, 41(2-3), 115-128.
[] [PMID: 20195797]
Hickman, S.; Izzy, S.; Sen, P.; Morsett, L.; El Khoury, J. Microglia in neurodegeneration. Nat. Neurosci., 2018, 21(10), 1359-1369.
[] [PMID: 30258234]
Bachiller, S.; Jiménez-Ferrer, I.; Paulus, A.; Yang, Y.; Swanberg, M.; Deierborg, T.; Boza-Serrano, A. Microglia in neurological Diseases: A road map to brain-disease dependent-inflammatory response. Front. Cell. Neurosci., 2018, 12, 488.
[] [PMID: 30618635]
Chen, Y-C.; Wu, J-S.; Tsai, H-D.; Huang, C-Y.; Chen, J-J.; Sun, G.Y.; Lin, T-N. Peroxisome proliferator-activated receptor gamma (PPAR-γ) and neurodegenerative disorders. Mol. Neurobiol., 2012, 46(1), 114-124.
[] [PMID: 22434581]
Cai, Z.; Hussain, M.D.; Yan, L-J. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. Int. J. Neurosci., 2014, 124(5), 307-321.
[] [PMID: 23930978]
Edwards, F.A. A Unifying hypothesis for Alzheimer’s disease: From plaques to neurodegeneration. Trends Neurosci., 2019, 42(5), 310-322.
[] [PMID: 31006494]
Knopman, D.S.; Parisi, J.E.; Salviati, A.; Floriach-Robert, M.; Boeve, B.F.; Ivnik, R.J.; Smith, G.E.; Dickson, D.W.; Johnson, K.A.; Petersen, L.E.; McDonald, W.C.; Braak, H.; Petersen, R.C. Neuropathology of cognitively normal elderly., J. Neuropathol. Exp. Neurol., 2003, 62(11 PG-1087-95), 1087-1095.
Attems, J.; Jellinger, K.A. The overlap between vascular disease and Alzheimer’s disease--lessons from pathology. BMC Med., 2014, 12(1), 206.
[] [PMID: 25385447]
Fazekas, F.; Gattringer, T.; Enzinger, C. Cerebrovascular disorders. Curr. Opin. Neurol., 2018, 31(4), 345-353.
[] [PMID: 29878907]
Hase, Y.; Horsburgh, K.; Ihara, M.; Kalaria, R.N. White matter degeneration in vascular and other ageing-related dementias. J. Neurochem., 2018, 144(5), 617-633.
[] [PMID: 29210074]
Jellinger, K.A.; Attems, J. Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease. J. Neurol. Sci., 2005, 229-230, 37-41.
[] [PMID: 15760617]
Schneider, J.A.; Wilson, R.S.; Bienias, J.L.; Evans, D.A.; Bennett, D.A. Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology, 2004, 62(7), 1148-1155.
[] [PMID: 15079015]
Kapasi, A.; Schneider, J.A. Vascular contributions to cognitive impairment, clinical Alzheimer’s disease, and dementia in older persons. Biochim. Biophys. Acta, 2016, 1862(5), 878-886.
[] [PMID: 26769363]
Raz, L.; Knoefel, J.; Bhaskar, K. The neuropathology and cerebrovascular mechanisms of dementia. J. Cereb. Blood Flow Metab., 2016, 36(1), 172-186.
[] [PMID: 26174330]
Smith, E.E. Clinical presentations and epidemiology of vascular dementia. Clin. Sci. (Lond.), 2017, 131(11), 1059-1068.
[] [PMID: 28515342]
O’Brien, J.T.; Thomas, A. Vascular dementia. Lancet, 2015, 386(10004), 1698-1706.
[] [PMID: 26595643]
Rodríguez García, P.L.; Rodríguez García, D. Diagnóstico Del Deterioro Cognitivo Vascular y Sus Principales Categorías. Neurologia, 2015, 30(4), 223-239.
[] [PMID: 22739039]
Schneider, J.A.; Arvanitakis, Z.; Bang, W.; Bennett, D.A. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, 2007, 69(24), 2197-2204.
[] [PMID: 17568013]
Nucera, A.; Hachinski, V. Cerebrovascular and Alzheimer disease: fellow travelers or partners in crime? J. Neurochem., 2018, 144(5), 513-516.
[] [PMID: 29266273]
van Norden, A.G.W.; van Dijk, E.J.; de Laat, K.F.; Scheltens, P.; Olderikkert, M.G.; de Leeuw, F.E. Dementia: Alzheimer pathology and vascular factors: from mutually exclusive to interaction. Biochim. Biophys. Acta, 2012, 1822(3), 340-349.
[] [PMID: 21777675]
Binnewijzend, M.A.A.; Kuijer, J.P.A.; van der Flier, W.M.; Benedictus, M.R.; Möller, C.M.; Pijnenburg, Y.A.L.; Lemstra, A.W.; Prins, N.D.; Wattjes, M.P.; van Berckel, B.N.M.; Scheltens, P.; Barkhof, F. Distinct perfusion patterns in Alzheimer’s disease, frontotemporal dementia and dementia with Lewy bodies. Eur. Radiol., 2014, 24(9), 2326-2333.
[] [PMID: 24996793]
Love, S.; Miners, J.S. Cerebral hypoperfusion and the energy deficit in Alzheimer’s disease. Brain Pathol., 2016, 26(5), 607-617.
[] [PMID: 27327656]
Tarumi, T.; Zhang, R. Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. J. Neurochem., 2018, 144(5), 595-608.
[] [PMID: 28986925]
Hays, C.C.; Zlatar, Z.Z.; Wierenga, C.E. The utility of cerebral blood flow as a biomarker of preclinical Alzheimer’s disease. Cell. Mol. Neurobiol., 2016, 36(2), 167-179.
[] [PMID: 26898552]
Love, S.; Miners, J.S. Cerebrovascular disease in ageing and Alzheimer’s disease. Acta Neuropathol., 2016, 131(5), 645-658.
[] [PMID: 26711459]
Kelleher, R.J.; Soiza, R.L. Evidence of endothelial dysfunction in the development of AD. Is AD a vascular disorder? Am. J. Cardiovasc. Dis., 2013, 3(4), 197-226.,
[PMID: 24224133]
Zlokovic, B.V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci., 2011, 12(12), 723-738.
[] [PMID: 22048062]
Kisler, K.; Nelson, A.R.; Montagne, A.; Zlokovic, B.V. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat. Rev. Neurosci., 2017, 18(7), 419-434.
[] [PMID: 28515434]
Bell, R.D.; Zlokovic, B.V. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol., 2009, 118(1), 103-113.
[] [PMID: 19319544]
Smoliński, Ł.; Członkowska, A. Cerebral vasomotor reactivity in neurodegenerative diseases. Neurol. Neurochir. Pol., 2016, 50(6), 455-462.
[] [PMID: 27553189]
Di Marco, L.Y.; Farkas, E.; Martin, C.; Venneri, A.; Frangi, A.F. Is vasomotion in cerebral arteries impaired in Alzheimer’s disease? J. Alzheimers Dis., 2015, 46(1), 35-53.
[] [PMID: 25720414]
Van Beek, A.H.E.A.; Claassen, J.A.H.R. The cerebrovascular role of the cholinergic neural system in Alzheimer’s disease. Behav. Brain Res., 2011, 221(2), 537-542.
[] [PMID: 20060023]
Claassen, J.; Jansen, R. Cholinergically mediated augmentation of cerebral perfusion in Alzheimer's disease and related cognitive disorders: The cholinergic-vascular hypothesis. J. Gerontol. Ser. A Biol. Med., 2006, 61(3), 267-271.
[PMID: 16567376]
Sweeney, M.D.; Zhao, Z.; Montagne, A.; Nelson, A.R.; Zlokovic, B.V. Blood-brain barrier: From physiology to disease and back. Physiol. Rev., 2019, 99(1), 21-78.
[] [PMID: 30280653]
Sweeney, M.D.; Sagare, A.P.; Zlokovic, B.V. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol., 2018, 14(3), 133-150.
[] [PMID: 29377008]
Chakraborty, A.; de Wit, N.M.; van der Flier, W.M.; de Vries, H.E. The blood brain barrier in Alzheimer’s disease. Vascul. Pharmacol., 2017, 89(4), 12-18.
[] [PMID: 27894893]
Rius-Pérez, S.; Tormos, A.M.; Pérez, S.; Taléns-Visconti, R. Patología Vascular: ¿causa o Efecto En La Enfermedad de Alzheimer? Neurologia, 2018, 33(2), 121-128.
[] [PMID: 26410024]
de la Torre, J. The vascular hypothesis of Alzheimer’s disease: A key to preclinical prediction of dementia using neuroimaging. J. Alzheimers Dis., 2018, 63(1), 35-52.
[] [PMID: 29614675]
Nelson, A.R.; Sweeney, M.D.; Sagare, A.P.; Zlokovic, B.V. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease. Biochim. Biophys. Acta, 2016, 1862(5), 887-900.
[] [PMID: 26705676]
Janota, C.; Lemere, C.A.; Brito, M.A. Dissecting the contribution of vascular alterations and aging to Alzheimer’s disease. Mol. Neurobiol., 2016, 53(6), 3793-3811.
[] [PMID: 26143259]
Saxena, T.; Ali, A.O.; Saxena, M. Pathophysiology of essential hypertension: an update. Expert Rev. Cardiovasc. Ther., 2018, 16(12), 879-887.
[] [PMID: 30354851]
Hall, J.E.; Granger, J.P.; do Carmo, J.M.; da Silva, A.A.; Dubinion, J.; George, E.; Hamza, S.; Speed, J.; Hall, M.E. Hypertension: physiology and pathophysiology. Comprehensive. Physiol., 2012, 2, 2393-2442.
Albaghdadi, M. Baroreflex control of long-term arterial pressure. Rev. Bras Hipertens, 2007, 14(4), 212-225.
Taler, S.J. Initial treatment of hypertension. N. Engl. J. Med., 2018, 378(7), 636-644.
[] [PMID: 29443671]
Yannoutsos, A.; Levy, B.I.; Safar, M.E.; Slama, G.; Blacher, J. Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction. J. Hypertens., 2014, 32(2), 216-224.
[] [PMID: 24270179]
Forrester, S.J.; Booz, G.W.; Sigmund, C.D.; Coffman, T.M.; Kawai, T.; Rizzo, V.; Scalia, R.; Eguchi, S.; Angiotensin, I.I. Angiotensin II signal transduction: An update on mechanisms of physiology and pathophysiology. Physiol. Rev., 2018, 98(3), 1627-1738.
[] [PMID: 29873596]
Harvey, A.; Montezano, A.C.; Lopes, R.A.; Rios, F.; Touyz, R.M. Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications. Can. J. Cardiol., 2016, 32(5), 659-668.
[] [PMID: 27118293]
Rodriguez-Iturbe, B.; Pons, H.; Johnson, R.J. Role of the immune system in hypertension. Physiol. Rev., 2017, 97(3), 1127-1164.
[] [PMID: 28566539]
Biancardi, V.C.; Stern, J.E. Compromised blood-brain barrier permeability: novel mechanism by which circulating angiotensin II signals to sympathoexcitatory centres during hypertension. J. Physiol., 2016, 594(6), 1591-1600.
[] [PMID: 26580484]
Setiadi, A.; Korim, W.S.; Elsaafien, K.; Yao, S.T. The role of the blood-brain barrier in hypertension. Exp. Physiol., 2018, 103(3), 337-342.
[] [PMID: 28986948]
Veglio, F.; Paglieri, C.; Rabbia, F.; Bisbocci, D.; Bergui, M.; Cerrato, P. Hypertension and cerebrovascular damage. Atherosclerosis, 2009, 205(2), 331-341.
[] [PMID: 19100549]
Walker, K.A.; Power, M.C.; Gottesman, R.F. Defining the relationship between hypertension, cognitive decline, and dementia: A review. Curr. Hypertens. Rep., 2017, 19(3), 24.
[] [PMID: 28299725]
Gąsecki, D.; Kwarciany, M.; Nyka, W.; Narkiewicz, K. Hypertension, brain damage and cognitive decline. Curr. Hypertens. Rep., 2013, 15(6), 547-558.
[] [PMID: 24146223]
Rimoldi, S.F.; Scherrer, U.; Messerli, F.H. Secondary arterial hypertension: when, who, and how to screen? Eur. Heart J., 2014, 35(19), 1245-1254.
[] [PMID: 24366917]
Kithas, P.A.; Supiano, M.A. Hypertension in the geriatric population: a patient-centered approach. Med. Clin. North Am., 2015, 99(2), 379-389.
[] [PMID: 25700589]
Setters, B.; Holmes, H.M. Hypertension in the older adult. Prim. Care, 2017, 44(3), 529-539.
[] [PMID: 28797378]
Franklin, S.S. Elderly hypertensives: how are they different? J. Clin. Hypertens. (Greenwich), 2012, 14(11), 779-786.
[] [PMID: 23126350]
Masters, C.L.; Bateman, R.; Blennow, K.; Rowe, C.C.; Sperling, R.A.; Cummings, J.L. Alzheimer’s disease. Nat. Rev. Dis. Primers, 2015, 1(1), 15056.
[] [PMID: 27188934]
Ballard, C.; Gauthier, S.; Corbett, A.; Brayne, C.; Aarsland, D.; Jones, E. Alzheimer’s disease. Lancet, 2011, 377(9770), 1019-1031.
[] [PMID: 21371747]
Silva, M.V.F.; Loures, C.M.G.; Alves, L.C.V.; de Souza, L.C.; Borges, K.B.G.; Carvalho, M.D.G. Alzheimer’s disease: risk factors and potentially protective measures. J. Biomed. Sci., 2019, 26(1), 33.
[] [PMID: 31072403]
Duron, E.; Hanon, O. Hypertension, cognitive decline and dementia. Arch. Cardiovasc. Dis. 2008, 2008, (101), 181-189.
Idiaquez, J.; Roman, G.C. Autonomic dysfunction in neurodegenerative dementias. J. Neurol. Sci., 2011, 305(1-2), 22-27.
[] [PMID: 21440258]
Skoog, I.; Lernfelt, B.; Landahl, S.; Palmertz, B.; Andreasson, L.A.; Nilsson, L.; Persson, G.; Odén, A.; Svanborg, A. 15-year longitudinal study of blood pressure and dementia. Lancet, 1996, 347(9009), 1141-1145.
[] [PMID: 8609748]
Meel-van den Abeelen, A.S.S.; Lagro, J.; Gommer, E.D.; Reulen, J.P.H.; Claassen, J.A.H.R. Baroreflex function is reduced in Alzheimer’s disease: a candidate biomarker? Neurobiol. Aging, 2013, 34(4), 1170-1176.
[] [PMID: 23140588]
Femminella, G.D.; Rengo, G.; Komici, K.; Iacotucci, P.; Petraglia, L.; Pagano, G.; de Lucia, C.; Canonico, V.; Bonaduce, D.; Leosco, D.; Ferrara, N. Autonomic dysfunction in Alzheimer’s disease: tools for assessment and review of the literature. J. Alzheimers Dis., 2014, 42(2), 369-377.
[] [PMID: 24898649]
Collins, O.; Dillon, S.; Finucane, C.; Lawlor, B.; Kenny, R.A. Parasympathetic autonomic dysfunction is common in mild cognitive impairment. Neurobiol. Aging, 2012, 33(10), 2324-2333.
[] [PMID: 22188719]
Jensen-Dahm, C.; Waldemar, G.; Staehelin Jensen, T.; Malmqvist, L.; Moeller, M.M.; Andersen, B.B.; Høgh, P.; Ballegaard, M. Autonomic dysfunction in patients with mild to moderate Alzheimer’s disease. J. Alzheimers Dis., 2015, 47(3), 681-689.
[] [PMID: 26401703]
Joas, E.; Bäckman, K.; Gustafson, D.; Östling, S.; Waern, M.; Guo, X.; Skoog, I. Blood pressure trajectories from midlife to late life in relation to dementia in women followed for 37 years. Hypertension, 2012, 59(4), 796-801.
[] [PMID: 22331381]
Launer, L.J.; Ross, G.W.; Petrovitch, H.; Masaki, K.; Foley, D.; White, L.R.; Havlik, R.J. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol. Aging, 2000, 21(1), 49-55.
[] [PMID: 10794848]
Sharp, S.I.; Aarsland, D.; Day, S.; Sønnesyn, H.; Ballard, C. Hypertension is a potential risk factor for vascular dementia: systematic review. Int. J. Geriatr. Psychiatry, 2011, 26(7), 661-669.
[] [PMID: 21495075]
Merkler, A.E.; Iadecola, C. Rollercoaster blood pressure: An Alzheimer disease risk factor? Circulation, 2017, 136(6), 526-528.
[] [PMID: 28784823]
Kuyumcu, M.E.; Yesil, Y.; Oztürk, Z.A.; Halil, M.; Ulger, Z.; Yavuz, B.B.; Cankurtaran, M.; Cınar, E.; Arıoğul, S. Alzheimer’s disease is associated with a low prevalence of hypertension. Dement. Geriatr. Cogn. Disord., 2012, 33(1), 6-10.
[] [PMID: 22354077]
Moonga, I.; Niccolini, F.; Wilson, H.; Pagano, G.; Politis, M. Hypertension is associated with worse cognitive function and hippocampal hypometabolism in Alzheimer’s disease. Eur. J. Neurol., 2017, 24(9), 1173-1182.
[] [PMID: 28752644]
Nation, D.A.; Delano-Wood, L.; Bangen, K.J.; Wierenga, C.E.; Jak, A.J.; Hansen, L.A.; Galasko, D.R.; Salmon, D.P.; Bondi, M.W. Antemortem pulse pressure elevation predicts cerebrovascular disease in autopsy-confirmed Alzheimer’s disease. J. Alzheimers Dis., 2012, 30(3), 595-603.
[] [PMID: 22451309]
Nelson, L.; Gard, P.; Tabet, N. Hypertension and inflammation in Alzheimer’s disease: close partners in disease development and progression! J. Alzheimers Dis., 2014, 41(2), 331-343.
[] [PMID: 24614908]
Carnevale, D.; Perrotta, M.; Lembo, G.; Trimarco, B. Pathophysiological links among hypertension and Alzheimer’s disease. High Blood Press. Cardiovasc. Prev., 2016, 23(1), 3-7.
[] [PMID: 26054481]
Mosterd, A.; Hoes, A.W. Clinical epidemiology of heart failure. Heart, 2007, 93(9), 1137-1146.
[] [PMID: 17699180]
Mann, D.L.; Bristow, M.R. Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation, 2005, 111(21), 2837-2849.
[] [PMID: 15927992]
Hartupee, J.; Mann, D.L. Neurohormonal activation in heart failure with reduced ejection fraction. Nat. Rev. Cardiol., 2017, 14(1), 30-38.
[] [PMID: 27708278]
van de Wal, R.M.A.; Plokker, H.W.M.; Lok, D.J.A.; Boomsma, F.; van der Horst, F.A.L.; van Veldhuisen, D.J.; van Gilst, W.H.; Voors, A.A. Determinants of increased angiotensin II levels in severe chronic heart failure patients despite ACE inhibition. Int. J. Cardiol., 2006, 106(3), 367-372.
[] [PMID: 16337046]
de Bruijn, R.F.; Ikram, M.A. Cardiovascular risk factors and future risk of Alzheimer’s disease. BMC Med., 2014, 12(1), 130.
[] [PMID: 25385322]
Cermakova, P.; Eriksdotter, M.; Lund, L.H.; Winblad, B.; Religa, P.; Religa, D. Heart failure and Alzheimer’s disease. J. Intern. Med., 2015, 277(4), 406-425.
[] [PMID: 25041352]
American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care, 2018, 41(Suppl. 1), S13-S27.
[] [PMID: 29222373]
Dominici, F.P.; Burghi, V.; Muñoz, M.C.; Giani, J.F. Modulation of the action of insulin by angiotensin-(1-7). Clin. Sci. (Lond.), 2014, 126(9), 613-630.
[] [PMID: 24450744]
Rein, J.; Bader, M. Renin-angiotensin system in diabetes. Protein Pept. Lett., 2017, 24(9), 833-840.
[] [PMID: 28758590]
American Diabetes Association. 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2019. Diabetes Care, 2019, 42(Suppl. 1), S124-S138.
[] [PMID: 30559237]
American Diabetes Association. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2019. Diabetes Care, 2019, 42(Suppl. 1), S103-S123.
[] [PMID: 30559236]
Tian, S.; Han, J.; Huang, R.; Xia, W.; Sun, J.; Cai, R.; Dong, X.; Shen, Y.; Wang, S. Association of increased serum ACE activity with logical memory ability in type 2 diabetic patients with mild cognitive impairment. Front. Behav. Neurosci., 2016, 10(December), 239.
[] [PMID: 28066203]
Kullmann, S.; Heni, M.; Hallschmid, M.; Fritsche, A.; Preissl, H.; Häring, H.U. Brain insulin resistance at the crossroads of metabolic and cognitive disorders in humans. Physiol. Rev., 2016, 96(4), 1169-1209.
[] [PMID: 27489306]
Riederer, P.; Korczyn, A.D.; Ali, S.S.; Bajenaru, O.; Choi, M.S.; Chopp, M.; Dermanovic-Dobrota, V.; Grünblatt, E.; Jellinger, K.A.; Kamal, M.A.; Kamal, W.; Leszek, J.; Sheldrick-Michel, T.M.; Mushtaq, G.; Meglic, B.; Natovich, R.; Pirtosek, Z.; Rakusa, M.; Salkovic-Petrisic, M.; Schmidt, R.; Schmitt, A.; Sridhar, G.R.; Vécsei, L.; Wojszel, Z.B.; Yaman, H.; Zhang, Z.G.; Cukierman-Yaffe, T. The diabetic brain and cognition. J. Neural Transm. (Vienna), 2017, 124(11), 1431-1454.
[] [PMID: 28766040]
Kandimalla, R.; Thirumala, V.; Reddy, P.H. Is Alzheimer’s disease a Type 3 Diabetes? A critical appraisal. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(5), 1078-1089.
[] [PMID: 27567931]
Abner, E.L.; Nelson, P.T.; Kryscio, R.J.; Schmitt, F.A.; Fardo, D.W.; Woltjer, R.L.; Cairns, N.J.; Yu, L.; Dodge, H.H.; Xiong, C.; Masaki, K.; Tyas, S.L.; Bennett, D.A.; Schneider, J.A.; Arvanitakis, Z. Diabetes is associated with cerebrovascular but not Alzheimer’s disease neuropathology. Alzheimers Dement., 2016, 12(8), 882-889.
[] [PMID: 26812281]
Kalaria, R.N. Neurodegenerative disease: Diabetes, microvascular pathology and Alzheimer disease. Nat. Rev. Neurol., 2009, 5(6), 305-306.
[] [PMID: 19498432]
Chapter 1: Definition and classification of CKD. Kidney Int Suppl, 2013, 3(1), 19-62.
Webster, A.C.; Nagler, E.V.; Morton, R.L.; Masson, P. Chronic kidney disease. Lancet, 2017, 389(10075), 1238-1252.
[] [PMID: 27887750]
Hill, N.R.; Fatoba, S.T.; Oke, J.L.; Hirst, J.A.; O’Callaghan, C.A.; Lasserson, D.S.; Hobbs, F.D.R. Global prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS One, 2016, 11(7) e0158765
[] [PMID: 27383068]
Sternlicht, H.; Bakris, G.L. The kidney in hypertension. Med. Clin. North Am., 2017, 101(1), 207-217.
[] [PMID: 27884230]
Romagnani, P.; Remuzzi, G.; Glassock, R.; Levin, A.; Jager, K.J.; Tonelli, M.; Massy, Z.; Wanner, C.; Anders, H-J. Chronic kidney disease. Nat. Rev. Dis. Primers, 2017, 3(1), 17088.
[] [PMID: 29168475]
Saldanha da Silva, A.A.; Rodrigues Prestes, T.R.; Lauar, A.O.; Finotti, B.B.; Simoes E Silva, A.C. Renin angiotensin system and cytokines in chronic kidney disease: Clinical and experimental evidence. Protein Pept. Lett., 2017, 24(9), 799-808.
[] [PMID: 28820061]
Roberts, M.A.; Velkoska, E.; Ierino, F.L.; Burrell, L.M. Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease. Nephrol. Dial. Transplant., 2013, 28(9), 2287-2294.
[] [PMID: 23535224]
Soler, M.J.; Wysocki, J.; Batlle, D. ACE2 alterations in kidney disease. Nephrol. Dial. Transplant., 2013, 28(11), 2687-2697.
[] [PMID: 23956234]
Etgen, T.; Sander, D.; Bickel, H.; Förstl, H. Mild cognitive impairment and dementia: the importance of modifiable risk factors. Dtsch. Arztebl. Int., 2011, 108(44), 743-750.
[] [PMID: 22163250]
Deckers, K.; Camerino, I.; van Boxtel, M.P.J.; Verhey, F.R.J.; Irving, K.; Brayne, C.; Kivipelto, M.; Starr, J.M.; Yaffe, K.; de Leeuw, P.W.; Köhler, S. Dementia risk in renal dysfunction: A systematic review and meta-analysis of prospective studies. Neurology, 2017, 88(2), 198-208.
[] [PMID: 27974647]
Kitaguchi, N.; Kawaguchi, K.; Nakai, S.; Murakami, K.; Ito, S.; Hoshino, H.; Hori, H.; Ohashi, A.; Shimano, Y.; Suzuki, N.; Yuzawa, Y.; Mutoh, T.; Sugiyama, S. Reduction of Alzheimer’s disease amyloid-β in plasma by hemodialysis and its relation to cognitive functions. Blood Purif., 2011, 32(1), 57-62.
[] [PMID: 21346337]
Sakai, K.; Senda, T.; Hata, R.; Kuroda, M.; Hasegawa, M.; Kato, M.; Abe, M.; Kawaguchi, K.; Nakai, S.; Hiki, Y.; Yuzawa, Y.; Kitaguchi, N. Patients that have undergone hemodialysis exhibit lower amyloid deposition in the brain: Evidence supporting a therapeutic strategy for Alzheimer’s disease by removal of blood amyloid. J. Alzheimers Dis., 2016, 51(4), 997-1002.
[] [PMID: 26923028]
Liu, Y.H.; Xiang, Y.; Wang, Y.R.; Jiao, S.S.; Wang, Q.H.; Bu, X.L.; Zhu, C.; Yao, X.Q.; Giunta, B.; Tan, J.; Zhou, H.D.; Wang, Y.J. Association between serum amyloid-beta and renal functions: implications for roles of kidney in amyloid-beta clearance. Mol. Neurobiol., 2015, 52(1), 115-119.
[] [PMID: 25119777]
Gronewold, J.; Klafki, H.W.; Baldelli, E.; Kaltwasser, B.; Seidel, U.K.; Todica, O.; Volsek, M.; Haußmann, U.; Wiltfang, J.; Kribben, A.; Bruck, H.; Hermann, D.M. Factors responsible for plasma β-amyloid accumulation in chronic kidney disease. Mol. Neurobiol., 2016, 53(5), 3136-3145.
[] [PMID: 26019016]
Gronewold, J.; Todica, O.; Klafki, H.W.; Seidel, U.K.; Kaltwasser, B.; Wiltfang, J.; Kribben, A.; Bruck, H.; Hermann, D.M. Association of plasma β-amyloid with cognitive performance and decline in chronic kidney disease. Mol. Neurobiol., 2017, 54(9), 7194-7203.
[] [PMID: 27796755]
Sayed-Tabatabaei, F.A.; Oostra, B.A.; Isaacs, A.; van Duijn, C.M.; Witteman, J.C.M. ACE polymorphisms. Circ. Res., 2006, 98(9), 1123-1133.
[] [PMID: 16690893]
Crisan, D.; Carr, J. Angiotensin I-converting enzyme: genotype and disease associations. J. Mol. Diagn., 2000, 2(3), 105-115.
[] [PMID: 11229513]
Landrum, M.J.; Lee, J.M.; Benson, M.; Brown, G.R.; Chao, C.; Chitipiralla, S.; Gu, B.; Hart, J.; Hoffman, D.; Jang, W.; Karapetyan, K.; Katz, K.; Liu, C.; Maddipatla, Z.; Malheiro, A.; McDaniel, K.; Ovetsky, M.; Riley, G.; Zhou, G.; Holmes, J.B.; Kattman, B.L.; Maglott, D.R. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res., 2018, 46(D1), D1062-D1067.
[] [PMID: 29165669]
National Center for Biotechnology Information. ClinVar; [VCV000375659.1]. Available from: (Accessed Jul 10, 2019).
Kehoe, P.G.; Russ, C.; McIlory, S.; Williams, H.; Holmans, P.; Holmes, C.; Liolitsa, D.; Vahidassr, D.; Powell, J.; McGleenon, B.; Liddell, M.; Plomin, R.; Dynan, K.; Williams, N.; Neal, J.; Cairns, N.J.; Wilcock, G.; Passmore, P.; Lovestone, S.; Williams, J.; Owen, M.J. Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat. Genet., 1999, 21(1), 71-72. [2],
[ ] [PMID: 9916793]
Zhang, J.W.; Li, X.Q.; Zhang, Z.X.; Chen, D.; Zhao, H.L.; Wu, Y.N.; Qu, Q.M. Association between angiotensin-converting enzyme gene polymorphism and Alzheimer’s disease in a Chinese population. Dement. Geriatr. Cogn. Disord., 2005, 20(1), 52-56.
[] [PMID: 15832037]
Isbir, T.; Agaçhan, B.; Yilmaz, H.; Aydin, M.; Kara, I.; Eker, D.; Eker, E. Interaction between apolipoprotein-E and angiotensin-converting enzyme genotype in Alzheimer’s disease. Am. J. Alzheimers Dis. Other Demen., 2001, 16(4), 205-210.
[] [PMID: 11501342]
Kehoe, P.G.; Katzov, H.; Feuk, L.; Bennet, A.M.; Johansson, B.; Wiman, B.; de Faire, U.; Cairns, N.J.; Wilcock, G.K.; Brookes, A.J.; Blennow, K.; Prince, J.A. Haplotypes extending across ACE are associated with Alzheimer’s disease. Hum. Mol. Genet., 2003, 12(8), 859-867.
[] [PMID: 12668609]
Lehmann, D.J.; Cortina-Borja, M.; Warden, D.R.; Smith, A.D.; Sleegers, K.; Prince, J.A.; van Duijn, C.M.; Kehoe, P.G. Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am. J. Epidemiol., 2005, 162(4), 305-317.
[] [PMID: 16033878]
Uitterlinden, A.G. An introduction to genome-wide association studies: GWAS for dummies. Semin. Reprod. Med., 2016, 34(4), 196-204.
[] [PMID: 27513020]
Yang, J.; Zeng, J.; Goddard, M.E.; Wray, N.R.; Visscher, P.M. Concepts, estimation and interpretation of SNP-based heritability. Nat. Genet., 2017, 49(9), 1304-1310.
[] [PMID: 28854176]
Ricigliano, V.A.G.; Umeton, R.; Germinario, L.; Alma, E.; Briani, M.; Di Segni, N.; Montesanti, D.; Pierelli, G.; Cancrini, F.; Lomonaco, C.; Grassi, F.; Palmieri, G.; Salvetti, M. Contribution of genome-wide association studies to scientific research: a pragmatic approach to evaluate their impact. PLoS One, 2013, 8(8)e71198
[] [PMID: 23967165]
Marigorta, U.M.; Rodríguez, J.A.; Gibson, G.; Navarro, A. Replicability and prediction: Lessons and challenges from GWAS. Trends Genet., 2018, 34(7), 504-517.
[] [PMID: 29716745]
Pihlstrøm, L.; Wiethoff, S.; Houlden, H. Genetics of neurodegenerative diseases: an overview. Handb. Clin. Neurol., 2017, 145, 309-323.
Lambert, J.C.; Ibrahim-Verbaas, C.A.; Harold, D.; Naj, A.C.; Sims, R.; Bellenguez, C.; DeStafano, A.L.; Bis, J.C.; Beecham, G.W.; Grenier-Boley, B.; Russo, G.; Thorton-Wells, T.A.; Jones, N.; Smith, A.V.; Chouraki, V.; Thomas, C.; Ikram, M.A.; Zelenika, D.; Vardarajan, B.N.; Kamatani, Y.; Lin, C.F.; Gerrish, A.; Schmidt, H.; Kunkle, B.; Dunstan, M.L.; Ruiz, A.; Bihoreau, M.T.; Choi, S.H.; Reitz, C.; Pasquier, F.; Cruchaga, C.; Craig, D.; Amin, N.; Berr, C.; Lopez, O.L.; De Jager, P.L.; Deramecourt, V.; Johnston, J.A.; Evans, D.; Lovestone, S.; Letenneur, L.; Morón, F.J.; Rubinsztein, D.C.; Eiriksdottir, G.; Sleegers, K.; Goate, A.M.; Fiévet, N.; Huentelman, M.W.; Gill, M.; Brown, K.; Kamboh, M.I.; Keller, L.; Barberger-Gateau, P.; McGuiness, B.; Larson, E.B.; Green, R.; Myers, A.J.; Dufouil, C.; Todd, S.; Wallon, D.; Love, S.; Rogaeva, E.; Gallacher, J.; St George-Hyslop, P.; Clarimon, J.; Lleo, A.; Bayer, A.; Tsuang, D.W.; Yu, L.; Tsolaki, M.; Bossù, P.; Spalletta, G.; Proitsi, P.; Collinge, J.; Sorbi, S.; Sanchez-Garcia, F.; Fox, N.C.; Hardy, J.; Deniz Naranjo, M.C.; Bosco, P.; Clarke, R.; Brayne, C.; Galimberti, D.; Mancuso, M.; Matthews, F.; Moebus, S.; Mecocci, P.; Del Zompo, M.; Maier, W.; Hampel, H.; Pilotto, A.; Bullido, M.; Panza, F.; Caffarra, P.; Nacmias, B.; Gilbert, J.R.; Mayhaus, M.; Lannefelt, L.; Hakonarson, H.; Pichler, S.; Carrasquillo, M.M.; Ingelsson, M.; Beekly, D.; Alvarez, V.; Zou, F.; Valladares, O.; Younkin, S.G.; Coto, E.; Hamilton-Nelson, K.L.; Gu, W.; Razquin, C.; Pastor, P.; Mateo, I.; Owen, M.J.; Faber, K.M.; Jonsson, P.V.; Combarros, O.; O’Donovan, M.C.; Cantwell, L.B.; Soininen, H.; Blacker, D.; Mead, S.; Mosley, T.H., Jr; Bennett, D.A.; Harris, T.B.; Fratiglioni, L.; Holmes, C.; de Bruijn, R.F.; Passmore, P.; Montine, T.J.; Bettens, K.; Rotter, J.I.; Brice, A.; Morgan, K.; Foroud, T.M.; Kukull, W.A.; Hannequin, D.; Powell, J.F.; Nalls, M.A.; Ritchie, K.; Lunetta, K.L.; Kauwe, J.S.; Boerwinkle, E.; Riemenschneider, M.; Boada, M.; Hiltuenen, M.; Martin, E.R.; Schmidt, R.; Rujescu, D.; Wang, L.S.; Dartigues, J.F.; Mayeux, R.; Tzourio, C.; Hofman, A.; Nöthen, M.M.; Graff, C.; Psaty, B.M.; Jones, L.; Haines, J.L.; Holmans, P.A.; Lathrop, M.; Pericak-Vance, M.A.; Launer, L.J.; Farrer, L.A.; van Duijn, C.M.; Van Broeckhoven, C.; Moskvina, V.; Seshadri, S.; Williams, J.; Schellenberg, G.D.; Amouyel, P. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet., 2013, 45(12), 1452-1458.
[] [PMID: 24162737]
Goldstein, B.; Speth, R.C.; Trivedi, M. Renin-angiotensin system gene expression and neurodegenerative diseases. J. Renin Angiotensin Aldosterone Syst., 2016, 17(3)1470320316666750
[] [PMID: 27613758]
Kehoe, P.G. The coming of age of the angiotensin hypothesis in Alzheimer’s disease: Progress toward disease prevention and treatment? J. Alzheimers Dis., 2018, 62(3), 1443-1466.
[] [PMID: 29562545]
Fadista, J.; Manning, A.K.; Florez, J.C.; Groop, L. The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants. Eur. J. Hum. Genet., 2016, 24(8), 1202-1205.
[] [PMID: 26733288]
Kauwe, J.S.K.; Bailey, M.H.; Ridge, P.G.; Perry, R.; Wadsworth, M.E.; Hoyt, K.L.; Staley, L.A.; Karch, C.M.; Harari, O.; Cruchaga, C.; Ainscough, B.J.; Bales, K.; Pickering, E.H.; Bertelsen, S.; Fagan, A.M.; Holtzman, D.M.; Morris, J.C.; Goate, A.M. Genome-wide association study of CSF levels of 59 alzheimer’s disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation. PLoS Genet., 2014, 10(10)e1004758
[] [PMID: 25340798]
Belbin, O.; Brown, K.; Shi, H.; Medway, C.; Abraham, R.; Passmore, P.; Mann, D.; Smith, A.D.; Holmes, C.; McGuinness, B.; Craig, D.; Warden, D.; Heun, R.; Kölsch, H.; Love, S.; Kalsheker, N.; Williams, J.; Owen, M.J.; Carrasquillo, M.; Younkin, S.; Morgan, K.; Kehoe, P.G. A multi-center study of ACE and the risk of late-onset Alzheimer’s disease. J. Alzheimers Dis., 2011, 24(3), 587-597.
[] [PMID: 21297258]
Hu, J.; Igarashi, A.; Kamata, M.; Nakagawa, H. Angiotensin-converting enzyme degrades Alzheimer amyloid β-peptide (A β ); retards A β aggregation, deposition, fibril formation; and inhibits cytotoxicity. J. Biol. Chem., 2001, 276(51), 47863-47868.
[] [PMID: 11604391]
Oba, R.; Igarashi, A.; Kamata, M.; Nagata, K.; Takano, S.; Nakagawa, H. The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid β-peptide. Eur. J. Neurosci., 2005, 21(3), 733-740.
[] [PMID: 15733091]
Larmuth, K.M.; Masuyer, G.; Douglas, R.G.; Schwager, S.L.; Acharya, K.R.; Sturrock, E.D. Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme. FEBS J., 2016, 283(6), 1060-1076.
[] [PMID: 26748546]
Kugaevskaya, E.V.; Veselovsky, A.V.; Indeykina, M.I.; Solovyeva, N.I.; Zharkova, M.S.; Popov, I.A.; Nikolaev, E.N.; Mantsyzov, A.B.; Makarov, A.A.; Kozin, S.A. N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-β(1-16) peptides as arginine specific endopeptidase potentially enhancing risk of Alzheimer’s disease. Sci. Rep., 2018, 8(1), 298.
[] [PMID: 29321566]
Jalkute, C.B.; Barage, S.H.; Dhanavade, M.J.; Sonawane, K.D. Molecular dynamics simulation and molecular docking studies of Angiotensin converting enzyme with inhibitor lisinopril and amyloid Beta Peptide. Protein J., 2013, 32(5), 356-364.
[] [PMID: 23660814]
Hemming, M.L.; Selkoe, D.J. Amyloid β-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J. Biol. Chem., 2005, 280(45), 37644-37650.
[] [PMID: 16154999]
Zou, K.; Yamaguchi, H.; Akatsu, H.; Sakamoto, T.; Ko, M.; Mizoguchi, K.; Gong, J-S.; Yu, W.; Yamamoto, T.; Kosaka, K. Angiotensin-converting enzyme converts amyloid -protein 1 42 (A 1 42) to A 1 40, and its inhibition enhances brain a deposition. J. Neurosci., 2007, 27(32), 8628-8635.
[] [PMID: 17687040]
Zou, K.; Liu, J.; Watanabe, A.; Hiraga, S.; Liu, S.; Tanabe, C.; Maeda, T.; Terayama, Y.; Takahashi, S.; Michikawa, M.; Komano, H. Aβ43 is the earliest-depositing Aβ species in APP transgenic mouse brain and is converted to Aβ41 by two active domains of ACE. Am. J. Pathol., 2013, 182(6), 2322-2331.
[] [PMID: 23562443]
Liu, S.; Liu, J.; Miura, Y.; Tanabe, C.; Maeda, T.; Terayama, Y.; Turner, A.J.; Zou, K.; Komano, H. Conversion of Aβ43 to Aβ40 by the successive action of angiotensin-converting enzyme 2 and angiotensin-converting enzyme. J. Neurosci. Res., 2014, 92(9), 1178-1186.
[] [PMID: 24823497]
Saito, T.; Suemoto, T.; Brouwers, N.; Sleegers, K.; Funamoto, S.; Mihira, N.; Matsuba, Y.; Yamada, K.; Nilsson, P.; Takano, J.; Nishimura, M.; Iwata, N.; Van Broeckhoven, C.; Ihara, Y.; Saido, T.C. Potent amyloidogenicity and pathogenicity of Aβ43. Nat. Neurosci., 2011, 14(8), 1023-1032.
[] [PMID: 21725313]
Bernstein, K.E.; Koronyo, Y.; Salumbides, B.C.; Sheyn, J.; Pelissier, L.; Lopes, D.H.J.; Shah, K.H.; Bernstein, E.A.; Fuchs, D.T.; Yu, J.J.Y.; Pham, M.; Black, K.L.; Shen, X.Z.; Fuchs, S.; Koronyo-Hamaoui, M. Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline. J. Clin. Invest., 2014, 124(3), 1000-1012.
[] [PMID: 24487585]
Eckman, E.A.; Adams, S.K.; Troendle, F.J.; Stodola, B.A.; Kahn, M.A.; Fauq, A.H.; Xiao, H.D.; Bernstein, K.E.; Eckman, C.B. Regulation of steady-state β-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme. J. Biol. Chem., 2006, 281(41), 30471-30478.
[] [PMID: 16912050]
Hemming, M.L.; Selkoe, D.J.; Farris, W. Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid β-protein metabolism in mouse models of Alzheimer disease. Neurobiol. Dis., 2007, 26(1), 273-281.
[] [PMID: 17321748]
Baranello, R.J.; Bharani, K.L.; Padmaraju, V.; Chopra, N.; Lahiri, D.K.; Greig, N.H.; Pappolla, M.A.; Sambamurti, K. Amyloid-β protein clearance and degradation (ABCD) pathways and their role in Alzheimer’s disease. Curr. Alzheimer Res., 2015, 12(1), 32-46.
[] [PMID: 25523424]
Miners, J.S.; Palmer, J.C.; Tayler, H.; Palmer, L.E.; Ashby, E.; Kehoe, P.G.; Love, S. Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes. Front. Aging Neurosci., 2014, 6(SEP), 238.
[] [PMID: 25309424]
Zhu, D.; Shi, J.; Zhang, Y.; Wang, B.; Liu, W.; Chen, Z.; Tong, Q. Central angiotensin II stimulation promotes β amyloid production in Sprague Dawley rats. PLoS One, 2011, 6(1)e16037
[] [PMID: 21297982]
Wang, B.R.; Shi, J.Q.; Zhang, Y.D.; Zhu, D.L.; Shi, J.P.; Angiotensin, I.I. Angiotensin II does not directly affect Aβ secretion or β-/γ-secretase activity via activation of angiotensin II type 1 receptor. Neurosci. Lett., 2011, 500(2), 103-107.
[] [PMID: 21704122]
Kanarek, A.M.; Wagner, A.; Küppers, J.; Gütschow, M.; Postina, R.; Kojro, E. Crosstalk between angiotensin and the nonamyloidogenic pathway of Alzheimer’s amyloid precursor protein. FEBS J., 2017, 284(5), 742-753.
[] [PMID: 28102934]
Tian, M.; Zhu, D.; Xie, W.; Shi, J. Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains. FEBS Lett., 2012, 586(20), 3737-3745.
[] [PMID: 22982863]
Jiang, T.; Zhang, Y.D.; Zhou, J.S.; Zhu, X.C.; Tian, Y.Y.; Zhao, H.D.; Lu, H.; Gao, Q.; Tan, L.; Yu, J.T. Angiotensin-(1-7) is reduced and inversely correlates with tau hyperphosphorylation in animal models of Alzheimer’s disease. Mol. Neurobiol., 2016, 53(4), 2489-2497.
[] [PMID: 26044748]
Miranda, A.S.; Cordeiro, T.M.; Dos Santos Lacerda Soares, T.M.; Ferreira, R.N.; Simões E Silva, A.C. Kidney-brain axis inflammatory cross-talk: from bench to bedside. Clin. Sci. (Lond.), 2017, 131(11), 1093-1105.
[] [PMID: 28515344]
Garrido-Gil, P.; Joglar, B.; Rodriguez-Perez, A.I.; Guerra, M.J.; Labandeira-Garcia, J.L. Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson’s disease. J. Neuroinflammation, 2012, 9(1), 38.
[] [PMID: 22356806]
Carvalho, C.; Moreira, P.I. Oxidative stress: A major player in cerebrovascular alterations associated to neurodegenerative events. Front. Physiol., 2018, 9, 806.
[] [PMID: 30018565]
Costarelli, L.; Malavolta, M.; Giacconi, R.; Provinciali, M. Dysfunctional macrophages in Alzheimer Disease: another piece of the “macroph-aging” puzzle? Aging (Albany NY), 2017, 9(8), 1865-1866.
[] [PMID: 28783709]
Mammana, S.; Fagone, P.; Cavalli, E.; Basile, M.S.; Petralia, M.C.; Nicoletti, F.; Bramanti, P.; Mazzon, E. The role of macrophages in neuroinflammatory and neurodegenerative pathways of Alzheimer’s disease, amyotrophic lateral sclerosis, and multiple sclerosis: Pathogenetic cellular effectors and potential therapeutic targets. Int. J. Mol. Sci., 2018, 19(3), 1-20.
[] [PMID: 29533975]
Harrison, D.G.; Guzik, T.J. Macrophages come to mind as keys to cognitive decline. J. Clin. Invest., 2016, 126(12), 4393-4395.
[] [PMID: 27841765]
Faraco, G.; Sugiyama, Y.; Lane, D.; Garcia-Bonilla, L.; Chang, H.; Santisteban, M.M.; Racchumi, G.; Murphy, M.; Van Rooijen, N.; Anrather, J.; Iadecola, C. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J. Clin. Invest., 2016, 126(12), 4674-4689.
[] [PMID: 27841763]
Mowry, F.E.; Biancardi, V.C. Neuroinflammation in hypertension: the renin-angiotensin system versus pro-resolution pathways. Pharmacol. Res., 2019, 144, 279-291.
[] [PMID: 31039397]
Wang, Q-G.; Xue, X.; Yang, Y.; Gong, P-Y.; Jiang, T.; Zhang, Y-D. Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion. J. Renin Angiotensin Aldosterone Syst., 2018, 19(3)1470320318799587
[] [PMID: 30223703]
Liu, M.; Shi, P.; Sumners, C. Direct anti-inflammatory effects of angiotensin-(1-7) on microglia. J. Neurochem., 2016, 136(1), 163-171.
[] [PMID: 26448556]
Jiang, T.; Xue, L-J.; Yang, Y.; Wang, Q-G.; Xue, X.; Ou, Z.; Gao, Q.; Shi, J-Q.; Wu, L.; Zhang, Y-D. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation. Aging (Albany NY), 2018, 10(4), 645-657.
[] [PMID: 29667931]
Gallo-Payet, N.; Guimond, M.O.; Bilodeau, L.; Wallinder, C.; Alterman, M.; Hallberg, A. Angiotensin II, a neuropeptide at the frontier between endocrinology and neuroscience: Is there a link between the Angiotensin II type 2 receptor and Alzheimer’s disease? Front. Endocrinol. (Lausanne), 2011, 2, 17.
[] [PMID: 22649365]
Horiuchi, M.; Mogi, M. Roles of AT2R in Cognitive Function.The Protective Arm of System the Renin-Angiotensin Functional Aspects and Therapeutic Implications; Unger, T.; Steckelings, U.M.; Santos, R.A.S., Eds.; Academic Press: London, 2015, pp. 67-70.
Mogi, M.; Horiuchi, M. Effect of angiotensin II type 2 receptor on stroke, cognitive impairment and neurodegenerative diseases. Geriatr. Gerontol. Int., 2013, 13(1), 13-18.
[] [PMID: 22726823]
Hay, M.; Vanderah, T.W.; Samareh-Jahani, F.; Constantopoulos, E.; Uprety, A.R.; Barnes, C.A.; Konhilas, J. Cognitive impairment in heart failure: A protective role for angiotensin-(1-7). Behav. Neurosci., 2017, 131(1), 99-114.
[] [PMID: 28054808]
Cao, C.; Hasegawa, Y.; Hayashi, K.; Takemoto, Y.; Kim-Mitsuyama, S. Chronic angiotensin 1-7 infusion prevents angiotensin-ii-induced cognitive dysfunction and skeletal muscle injury in a mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2019, 69(1), 297-309.
[] [PMID: 30958350]
Xie, W.; Zhu, D.; Ji, L.; Tian, M.; Xu, C.; Shi, J. Angiotensin-(1-7) improves cognitive function in rats with chronic cerebral hypoperfusion. Brain Res., 2014, 1573, 44-53.
[] [PMID: 24854124]
Chappell, M.C. Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute? Am. J. Physiol. Heart Circ. Physiol., 2016, 310(2), H137-H152.
[] [PMID: 26475588]
Ashby, E.L.; Miners, J.S.; Kehoe, P.G.; Love, S. Effects of hypertension and anti-hypertensive treatment on amyloid-β (Aβ) plaque load and Aβ-synthesizing and Aβ-degrading enzymes in frontal cortex. J. Alzheimers Dis., 2016, 50(4), 1191-1203.
[] [PMID: 26836178]
Miners, S.; Ashby, E.; Baig, S.; Harrison, R.; Tayler, H.; Speedy, E.; Prince, J.A.; Love, S.; Kehoe, P.G. Angiotensin-converting enzyme levels and activity in Alzheimer’s disease: Differences in brain and CSF ACE and association with ACE1 genotypes. Am. J. Transl. Res., 2009, 1(2), 163-177.
[PMID: 19956428]
Mattsson, N.; Insel, P.; Nosheny, R.; Zetterberg, H.; Trojanowski, J.Q.; Shaw, L.M.; Tosun, D.; Weiner, M. CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders. Transl. Psychiatry, 2013, 3(July)e293
[] [PMID: 23962923]
Rocha, N.P.; Toledo, A.; Corgosinho, L.T.S.; de Souza, L.C.; Guimarães, H.C.; Resende, E.P.F.; Braz, N.F.T.; Gomes, K.B.; Simoes E Silva, A.C.; Caramelli, P.; Teixeira, A.L. Cerebrospinal fluid levels of angiotensin-converting enzyme are associated with amyloid-β42 burden in Alzheimer’s disease. J. Alzheimers Dis., 2018, 64(4), 1085-1090.
[] [PMID: 30040721]
Jochemsen, H.M.; Teunissen, C.E.; Ashby, E.L.; van der Flier, W.M.; Jones, R.E.; Geerlings, M.I.; Scheltens, P.; Kehoe, P.G.; Muller, M. The association of angiotensin-converting enzyme with biomarkers for Alzheimer’s disease. Alzheimers Res. Ther., 2014, 6(3), 27.
[] [PMID: 24987467]
Jochemsen, H.M.; van der Flier, W.M.; Ashby, E.L.; Teunissen, C.E.; Jones, R.E.; Wattjes, M.P.; Scheltens, P.; Geerlings, M.I.; Kehoe, P.G.; Muller, M. Angiotensin-converting enzyme in cerebrospinal fluid and risk of brain atrophy. J. Alzheimers Dis., 2015, 44(1), 153-162.
[] [PMID: 25201786]
Jochemsen, H.M.; Geerlings, M.I.; Grool, A.M.; Vincken, K.L.; Mali, W.P.; van der Graaf, Y.; Muller, M. Angiotensin-converting enzyme and progression of white matter lesions and brain atrophy--the SMART-MR study. J. Alzheimers Dis., 2012, 29(1), 39-49.
[] [PMID: 22214784]
Xu, G.; Bai, F.; Lin, X.; Wang, Q.; Wu, Q.; Sun, S.; Jiang, C.; Liang, Q.; Gao, B. Association between antihypertensive drug use and the incidence of cognitive decline and dementia: A meta-analysis of prospective cohort studies. BioMed Res. Int., 2017, 20174368474
[] [PMID: 29094046]
Duron, E.; Hanon, O. Antihypertensive treatments, cognitive decline, and dementia. J. Alzheimers Dis., 2010, 20(3), 903-914.
[] [PMID: 20182022]
Marfany, A.; Sierra, C.; Camafort, M.; Doménech, M.; Coca, A. High blood pressure, Alzheimer disease and antihypertensive treatment. Panminerva Med., 2018, 60(1), 8-16.
[] [PMID: 29370675]
Crous-Bou, M.; Minguillón, C.; Gramunt, N.; Molinuevo, J.L. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimers Res. Ther., 2017, 9(1), 71.
[] [PMID: 28899416]
Shah, K.; Qureshi, S.U.; Johnson, M.; Parikh, N.; Schulz, P.E.; Kunik, M.E. Does use of antihypertensive drugs affect the incidence or progression of dementia? A systematic review. Am. J. Geriatr. Pharmacother., 2009, 7(5), 250-261.
[] [PMID: 19948301]
Rouch, L.; Cestac, P.; Hanon, O.; Cool, C.; Helmer, C.; Bouhanick, B.; Chamontin, B.; Dartigues, J.F.; Vellas, B.; Andrieu, S. Antihypertensive drugs, prevention of cognitive decline and dementia: a systematic review of observational studies, randomized controlled trials and meta-analyses, with discussion of potential mechanisms. CNS Drugs, 2015, 29(2), 113-130.
[] [PMID: 25700645]
Gorelick, P.B.; Furie, K.L.; Iadecola, C.; Smith, E.E.; Waddy, S.P.; Lloyd-Jones, D.M.; Bae, H.J.; Bauman, M.A.; Dichgans, M.; Duncan, P.W.; Girgus, M.; Howard, V.J.; Lazar, R.M.; Seshadri, S.; Testai, F.D.; van Gaal, S.; Yaffe, K.; Wasiak, H.; Zerna, C. Defining optimal brain health in adults: A presidential advisory from the American Heart Association/American Stroke Association. Stroke, 2017, 48(10), e284-e303.
[] [PMID: 28883125]
Iadecola, C.; Yaffe, K.; Biller, J.; Bratzke, L.C.; Faraci, F.M.; Gorelick, P.B.; Gulati, M.; Kamel, H.; Knopman, D.S.; Launer, L.J.; Saczynski, J.S.; Seshadri, S.; Zeki Al Hazzouri, A. Impact of hypertension on cognitive function: A scientific statement from the American Heart Association. Hypertension, 2016, 68(6), e67-e94.
[] [PMID: 27977393]
Staessen, J.A.; Richart, T.; Birkenhäger, W.H. Less atherosclerosis and lower blood pressure for a meaningful life perspective with more brain. Hypertension, 2007, 49(3), 389-400.
[] [PMID: 17283254]
van Middelaar, T.; van Vught, L.A.; Moll van Charante, E.P.; Eurelings, L.S.M.; Ligthart, S.A.; van Dalen, J.W.; van den Born, B.J.H.; Richard, E.; van Gool, W.A. Lower dementia risk with different classes of antihypertensive medication in older patients. J. Hypertens., 2017, 35(10), 2095-2101.
[] [PMID: 28509727]
Levi Marpillat, N.; Macquin-Mavier, I.; Tropeano, A.I.; Bachoud-Levi, A.C.; Maison, P. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J. Hypertens., 2013, 31(6), 1073-1082.
[] [PMID: 23552124]
Barthold, D.; Joyce, G.; Wharton, W.; Kehoe, P.; Zissimopoulos, J. The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity. PLoS One, 2018, 13(11)e0206705
[] [PMID: 30383807]
Zhuang, S.; Wang, H-F.; Wang, X.; Li, J.; Xing, C-M. The association of renin-angiotensin system blockade use with the risks of cognitive impairment of aging and Alzheimer’s disease: A meta-analysis. J. Clin. Neurosci., 2016, 33, 32-38.
[] [PMID: 27475317]
Ye, R.; Hu, Y.; Yao, A.; Yang, Y.; Shi, Y.; Jiang, Y.; Zhang, J. Impact of renin-angiotensin system-targeting antihypertensive drugs on treatment of Alzheimer’s disease: a meta-analysis. Int. J. Clin. Pract., 2015, 69(6), 674-681.
[] [PMID: 25721930]
Petek, B.; Villa-Lopez, M.; Loera-Valencia, R.; Gerenu, G.; Winblad, B.; Kramberger, M.G.; Ismail, M.A.M.; Eriksdotter, M.; Garcia-Ptacek, S. Connecting the brain cholesterol and renin-angiotensin systems: potential role of statins and RAS-modifying medications in dementia. J. Intern. Med., 2018, 284(6), 620-642.
[] [PMID: 30264910]
Ohrui, T.; Tomita, N.; Sato-Nakagawa, T.; Matsui, T.; Maruyama, M.; Niwa, K.; Arai, H.; Sasaki, H. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology, 2004, 63(7), 1324-1325.
[] [PMID: 15477567]
de Oliveira, F.F.; Bertolucci, P.H.F.; Chen, E.S.; Smith, M.C. Brain-penetrating angiotensin-converting enzyme inhibitors and cognitive change in patients with dementia due to Alzheimer’s disease. J. Alzheimers Dis., 2014, 42(Suppl. 3), S321-S324.
[] [PMID: 24577465]
O’Caoimh, R.; Healy, L.; Gao, Y.; Svendrovski, A.; Kerins, D.M.; Eustace, J.; Kehoe, P.G.; Guyatt, G.; Molloy, D.W. Effects of centrally acting angiotensin converting enzyme inhibitors on functional decline in patients with Alzheimer’s disease. J. Alzheimers Dis., 2014, 40(3), 595-603.
[] [PMID: 24496072]
Wharton, W.; Stein, J.H.; Korcarz, C.; Sachs, J.; Olson, S.R.; Zetterberg, H.; Dowling, M.; Ye, S.; Gleason, C.E.; Underbakke, G.; Jacobson, L.E.; Johnson, S.C.; Sager, M.A.; Asthana, S.; Carlsson, C.M. The effects of ramipril in individuals at risk for Alzheimer’s disease: results of a pilot clinical trial. J. Alzheimers Dis., 2012, 32(1), 147-156.
[] [PMID: 22776970]
Fazal, K.; Perera, G.; Khondoker, M.; Howard, R.; Stewart, R. Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer’s disease. BJPsych Open, 2017, 3(4), 158-164.
[] [PMID: 28713585]
Kume, K.; Hanyu, H.; Sakurai, H.; Takada, Y.; Onuma, T.; Iwamoto, T. Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer’s disease. Geriatr. Gerontol. Int., 2012, 12(2), 207-214.
[] [PMID: 21929736]
Wharton, W.; Goldstein, F.C.; Zhao, L.; Steenland, K.; Levey, A.I.; Hajjar, I. Modulation of renin-angiotensin system may slow conversion from mild cognitive impairment to Alzheimer’s disease. J. Am. Geriatr. Soc., 2015, 63(9), 1749-1756.
[] [PMID: 26389987]
Furiya, Y.; Ryo, M.; Kawahara, M.; Kiriyama, T.; Morikawa, M.; Ueno, S. Renin-angiotensin system blockers affect cognitive decline and serum adipocytokines in Alzheimer’s disease. Alzheimers Dement., 2013, 9(5), 512-518.
[] [PMID: 23142434]
Kehoe, P.G.; Blair, P.S.; Howden, B.; Thomas, D.L.; Malone, I.B.; Horwood, J.; Clement, C.; Selman, L.E.; Baber, H.; Lane, A.; Coulthard, E.; Passmore, A.P.; Fox, N.C.; Wilkinson, I.B.; Ben-Shlomo, Y. The rationale and design of the reducing pathology in Alzheimer’s disease through angiotensin targeting (RADAR) trial. J. Alzheimers Dis., 2018, 61(2), 803-814.
[] [PMID: 29226862]
Saavedra, J.M. Evidence to consider angiotensin II receptor blockers for the treatment of early Alzheimer’s disease. Cell. Mol. Neurobiol., 2016, 36(2), 259-279.
[] [PMID: 26993513]
Saavedra, J.M.; Sánchez-Lemus, E.; Benicky, J. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications. Psychoneuroendocrinology, 2011, 36(1), 1-18.
[] [PMID: 21035950]
Asraf, K.; Torika, N.; Apte, R.N.; Fleisher-Berkovich, S. Microglial activation is modulated by captopril: In vitro and in vivo studies. Front. Cell. Neurosci., 2018, 12(May), 116.
[] [PMID: 29765306]
Villapol, S.; Saavedra, J.M. Neuroprotective effects of angiotensin receptor blockers. Am. J. Hypertens., 2015, 28(3), 289-299.
[] [PMID: 25362113]
Erbe, D.V.; Gartrell, K.; Zhang, Y-L.; Suri, V.; Kirincich, S.J.; Will, S.; Perreault, M.; Wang, S.; Tobin, J.F. Molecular activation of PPARgamma by angiotensin II type 1-receptor antagonists. Vascul. Pharmacol., 2006, 45(3), 154-162.
[] [PMID: 16765099]
Zolezzi, J.M.; Santos, M.J.; Bastías-Candia, S.; Pinto, C.; Godoy, J.A.; Inestrosa, N.C. PPARs in the central nervous system: roles in neurodegeneration and neuroinflammation. Biol. Rev. Camb. Philos. Soc., 2017, 92(4), 2046-2069.
[] [PMID: 28220655]
Torika, N.; Asraf, K.; Apte, R.N.; Fleisher-Berkovich, S. Candesartan ameliorates brain inflammation associated with Alzheimer’s disease. CNS Neurosci. Ther., 2018, 24(3), 231-242.
[] [PMID: 29365370]
Ferrington, L.; Palmer, L.E.; Love, S.; Horsburgh, K.J.; Kelly, P.A.T.; Kehoe, P.G. Angiotensin II-inhibition: effect on Alzheimer’s pathology in the aged triple transgenic mouse. Am. J. Transl. Res., 2012, 4(2), 151-164.,
[PMID: 22611468]
Dong, Y-F.; Kataoka, K.; Tokutomi, Y.; Nako, H.; Nakamura, T.; Toyama, K.; Sueta, D.; Koibuchi, N.; Yamamoto, E.; Ogawa, H.; Kim-Mitsuyama, S. Perindopril, a centrally active angiotensin-converting enzyme inhibitor, prevents cognitive impairment in mouse models of Alzheimer’s disease. FASEB J., 2011, 25(9), 2911-2920.
[] [PMID: 21593435]
Ongali, B.; Nicolakakis, N.; Tong, X.K.; Aboulkassim, T.; Papadopoulos, P.; Rosa-Neto, P.; Lecrux, C.; Imboden, H.; Hamel, E.; Angiotensin, I.I. Angiotensin II type 1 receptor blocker losartan prevents and rescues cerebrovascular, neuropathological and cognitive deficits in an Alzheimer’s disease model. Neurobiol. Dis., 2014, 68, 126-136.
[] [PMID: 24807206]
Papadopoulos, P.; Tong, X.K.; Imboden, H.; Hamel, E. Losartan improves cerebrovascular function in a mouse model of Alzheimer’s disease with combined overproduction of amyloid-β and transforming growth factor-β1. J. Cereb. Blood Flow Metab., 2017, 37(6), 1959-1970.
[] [PMID: 27389178]
Wiesmann, M.; Roelofs, M.; van der Lugt, R.; Heerschap, A.; Kiliaan, A.J.; Claassen, J.A.H.R.; Angiotensin, I.I. Angiotensin II, hypertension and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer’s disease. J. Cereb. Blood Flow Metab., 2017, 37(7), 2396-2413.
[] [PMID: 27596834]
AbdAlla, S.; Langer, A.; Fu, X.; Quitterer, U. ACE inhibition with captopril retards the development of signs of neurodegeneration in an animal model of Alzheimer’s disease. Int. J. Mol. Sci., 2013, 14(8), 16917-16942.
[] [PMID: 23959119]
Götz, J.; Ittner, L.M. Animal models of Alzheimer’s disease and frontotemporal dementia. Nat. Rev. Neurosci., 2008, 9(7), 532-544.
[] [PMID: 18568014]
King, A. The search for better animal models of Alzheimer’s disease. Nature, 2018, 559(7715), S13-S15.
[] [PMID: 30046083]
Laurijssens, B.; Aujard, F.; Rahman, A. Animal models of Alzheimer’s disease and drug development. Drug Discov. Today. Technol., 2013, 10(3), e319-e327.
[] [PMID: 24050129]
Mhillaj, E.; Cuomo, V.; Mancuso, C. The Contribution of transgenic and nontransgenic animal models in Alzheimer’s disease drug research and development. Behav. Pharmacol., 2017, 28(2-3 Special Issue), 95-111.,
Neha, H.; Sodhi, R.K.; Jaggi, A.S.; Singh, N. Animal models of dementia and cognitive dysfunction. Life Sci., 2014, 109(2), 73-86.
[] [PMID: 25066372]
Braidy, N.; Poljak, A.; Jayasena, T.; Mansour, H.; Inestrosa, N.C.; Sachdev, P.S. Accelerating Alzheimer’s research through ‘natural’ animal models. Curr. Opin. Psychiatry, 2015, 28(2), 155-164.
[] [PMID: 25602247]
Puzzo, D.; Lee, L.; Palmeri, A.; Calabrese, G.; Arancio, O. Behavioral assays with mouse models of Alzheimer’s disease: practical considerations and guidelines. Biochem. Pharmacol., 2014, 88(4), 450-467.
[] [PMID: 24462904]
LaFerla, F.M.; Green, K.N. Animal models of Alzheimer disease. Cold Spring Harb. Perspect. Med., 2012, 2(11), a006320-a006320.
[] [PMID: 23002015]
Nicolakakis, N.; Hamel, E. Neurovascular function in Alzheimer’s disease patients and experimental models. J. Cereb. Blood Flow Metab., 2011, 31(6), 1354-1370.
[] [PMID: 21468088]
Kehoe, P.G.; Hibbs, E.; Palmer, L.E.; Miners, J.S. Angiotensin-III is increased in Alzheimer’s disease in association with amyloid-β and Tau pathology. J. Alzheimers Dis., 2017, 58(1), 203-214.
[] [PMID: 28387670]
Hyman, B.T.; Phelps, C.H.; Beach, T.G.; Bigio, E.H.; Cairns, N.J.; Carrillo, M.C.; Dickson, D.W.; Duyckaerts, C.; Frosch, M.P.; Masliah, E.; Mirra, S.S.; Nelson, P.T.; Schneider, J.A.; Thal, D.R.; Thies, B.; Trojanowski, J.Q.; Vinters, H.V.; Montine, T.J. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement., 2012, 8(1), 1-13.
[] [PMID: 22265587]
Kehoe, P.G.; Wong, S.; Al Mulhim, N.; Palmer, L.E.; Miners, J.S. Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology. Alzheimers Res. Ther., 2016, 8(1), 50.
[] [PMID: 27884212]
Miners, J.S.; Ashby, E.; Van Helmond, Z.; Chalmers, K.A.; Palmer, L.E.; Love, S.; Kehoe, P.G. Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer’s disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol. Appl. Neurobiol., 2008, 34(2), 181-193.
[] [PMID: 17973905]
Mirra, S.S.; Heyman, A.; McKeel, D.; Sumi, S.M.; Crain, B.J.; Brownlee, L.M.; Vogel, F.S.; Hughes, J.P.; van Belle, G.; Berg, L. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology, 1991, 41(4), 479-486.
[] [PMID: 2011243]
Savaskan, E.; Hock, C.; Olivieri, G.; Bruttel, S.; Rosenberg, C.; Hulette, C.; Müller-Spahn, F. Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer’s dementia. Neurobiol. Aging, 2001, 22(4), 541-546.
[] [PMID: 11445253]
Ge, J.; Barnes, N.M. Alterations in angiotensin AT1 and AT2 receptor subtype levels in brain regions from patients with neurodegenerative disorders. Eur. J. Pharmacol., 1996, 297(3), 299-306.
[] [PMID: 8666063]
Barnes, N.M.; Cheng, C.H.K.; Costall, B.; Naylor, R.J.; Williams, T.J.; Wischik, C.M. Angiotensin converting enzyme density is increased in temporal cortex from patients with Alzheimer’s disease. Eur. J. Pharmacol., 1991, 200(2-3), 289-292.
[] [PMID: 1664329]
Arregui, A.; Perry, E.K.; Rossor, M.; Tomlinson, B.E. Angiotensin converting enzyme in Alzheimer’s disease increased activity in caudate nucleus and cortical areas. J. Neurochem., 1982, 38(5), 1490-1492.
[] [PMID: 6278093]
Perry, E.K.; Tomlinson, B.E.; Blessed, G.; Bergmann, K.; Gibson, P.H.; Perry, R.H. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. BMJ, 1978, 2(6150), 1457-1459.
[] [PMID: 719462]
McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R., Jr; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; Mohs, R.C.; Morris, J.C.; Rossor, M.N.; Scheltens, P.; Carrillo, M.C.; Thies, B.; Weintraub, S.; Phelps, C.H. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement., 2011, 7(3), 263-269.
[] [PMID: 21514250]
Nielsen, H.M.; Londos, E.; Minthon, L.; Janciauskiene, S.M. Soluble adhesion molecules and angiotensin-converting enzyme in dementia. Neurobiol. Dis., 2007, 26(1), 27-35.
[] [PMID: 17270454]
He, M.; Ohrui, T.; Maruyama, M.; Tomita, N.; Nakayama, K.; Higuchi, M.; Furukawa, K.; Arai, H. ACE activity in CSF of patients with mild cognitive impairment and Alzheimer disease. Neurology, 2006, 67(7), 1309-1310.
[] [PMID: 17030780]
Petersen, R.C.; Doody, R.; Kurz, A.; Mohs, R.C.; Morris, J.C.; Rabins, P.V.; Ritchie, K.; Rossor, M.; Thal, L.; Winblad, B. Current concepts in mild cognitive impairment. Arch. Neurol., 2001, 58(12), 1985-1992.
[] [PMID: 11735772]
Zubenko, G.S.; Marquis, J.K.; Volicer, L.; Direnfeld, L.K.; Langlais, P.J.; Nixon, R.A. Cerebrospinal fluid levels of angiotensin-converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer’s disease and Parkinson’s disease: a correlative study. Biol. Psychiatry, 1986, 21(14), 1365-1381.
[] [PMID: 3024746]
Wells, C.E. Diagnostic evaluation and treatment in dementia., Contemp. Neurol. Ser., 1977, 15, 247-276.
[PMID: 923244]
Zubenko, G.S.; Volicer, L.; Direnfeld, L.K.; Freeman, M.; Langlais, P.J.; Nixon, R.A. Cerebrospinal fluid levels of angiotensin-converting enzyme in Alzheimer’s disease, Parkinson’s disease and progressive supranuclear palsy. Brain Res., 1985, 328(2), 215-221.
[] [PMID: 2985183]
Jiang, T.; Tan, L.; Gao, Q.; Lu, H.; Zhu, X.C.; Zhou, J.S.; Zhang, Y.D. Plasma angiotensin-(1-7) is a potential biomarker for Alzheimer’s disease. Curr. Neurovasc. Res., 2016, 13(2), 96-99.
[] [PMID: 26907614]
Gard, P.R.; Fidalgo, S.; Lotter, I.; Richardson, C.; Farina, N.; Rusted, J.; Tabet, N. Changes of renin-angiotensin system-related aminopeptidases in early stage Alzheimer’s disease. Exp. Gerontol., 2017, 89, 1-7.
[] [PMID: 28069385]
Zhuang, S.; Wang, X.; Wang, H.F.; Li, J.; Wang, H.Y.; Zhang, H.Z.; Xing, C.M. Angiotensin converting enzyme serum activities: Relationship with Alzheimer’s disease. Brain Res., 2016, 1650, 196-202.
[] [PMID: 27608957]
Petersen, R.C. Mild cognitive impairment as a diagnostic entity. J. Intern. Med., 2004, 256(3), 183-194.
[] [PMID: 15324362]
Puertas, M. del C.; Martínez-Martos, J.M.; Cobo, M.; Lorite, P.; Sandalio, R.M.; Palomeque, T.; Torres, M.I.; Carrera-González, M.P.; Mayas, M.D.; Ramírez-Expósito, M.J. Plasma renin-angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer’s disease and show gender differences but are not related to apolipoprotein E genotype. Exp. Gerontol., 2013, 48(6), 557-564.
[] [PMID: 23500679]
Bell, C.C. DSM-IV: Diagnostic and Statistical Manual of mental disorders. JAMA J. Am. Med. Assoc, 1994, 272(10), 828.
Akatsu, H.; Ogawa, N.; Kanesaka, T.; Hori, A.; Yamamoto, T.; Matsukawa, N.; Michikawa, M. Higher activity of peripheral blood angiotensin-converting enzyme is associated with later-onset of Alzheimer’s disease. J. Neurol. Sci., 2011, 300(1-2), 67-73.
[] [PMID: 21040931]
Heyman, A.; Peterson, B.; Fillenbaum, G.; Pieper, C. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part XIV: Demographic and clinical predictors of survival in patients with Alzheimer’s disease. Neurology, 1996, 46(3), 656-660.
[] [PMID: 8618662]
Vardy, E.R.L.C.; Rice, P.J.; Bowie, P.C.W.; Holmes, J.D.; Catto, A.J.; Hooper, N.M. Plasma angiotensin-converting enzyme in Alzheimer’s disease. J. Alzheimers Dis., 2009, 16(3), 609-618.
[] [PMID: 19276555]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy