Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Mini-Review Article

Cerebrovascular Changes and Neurodegeneration Related to Hyperlipidemia: Characteristics of the Human ApoB-100 Transgenic Mice

Author(s): Melinda E. Tóth*, Brigitta Dukay , Zsófia Hoyk and Miklós Sántha

Volume 26, Issue 13, 2020

Page: [1486 - 1494] Pages: 9

DOI: 10.2174/1381612826666200218101818

open access plus


Serum lipid levels are closely related to the structure and function of blood vessels. Chronic hyperlipidemia may lead to damage in both the cardio- and the cerebrovascular systems. Vascular dysfunctions, including impairments of the blood-brain barrier, are known to be associated with neurodegenerative diseases. A growing number of evidence suggests that cardiovascular risk factors, such as hyperlipidemia, may increase the likelihood of developing dementia. Due to differences in lipoprotein metabolism, wild-type mice are protected against dietinduced hypercholesterolemia, and their serum lipid profile is different from that observed in humans. Therefore, several transgenic mouse models have been established to study the role of different apolipoproteins and their receptors in lipid metabolism, as well as the complications related to pathological lipoprotein levels. This minireview focused on a transgenic mouse model overexpressing an apolipoprotein, the human ApoB-100. We discussed literature data and current advancements on the understanding of ApoB-100 induced cardio- and cerebrovascular lesions in order to demonstrate the involvement of this type of apolipoprotein in a wide range of pathologies, and a link between hyperlipidemia and neurodegeneration.

Keywords: ApoB-100 lipoprotein, hyperlipidemia, atherosclerosis, blood-brain barrier (BBB), endothelial dysfunction, cerebrovascular disease, neurodegeneration, dementia, transgenic mice.

Ramasamy I. Recent advances in physiological lipoprotein metabolism. Clin Chem Lab Med 2014; 52(12): 1695-727.
[] [PMID: 23940067]
Feingold KR, Grunfeld C. Introduction to lipids and lipoproteins. Endotext. Available at: ed/26247089
Shiomi M, Koike T, Ishi T. Genetically modified animal models for lipoprotein research.In: lipoproteins - role in health and diseases IntechOpen. 2012.
Greeve J, Altkemper I, Dieterich JH, Greten H, Windler E. Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins. J Lipid Res 1993; 34(8): 1367-83.
[PMID: 8409768]
Kim E, Young SG. Genetically modified mice for the study of apolipoprotein B. J Lipid Res 1998; 39(4): 703-23.
[PMID: 9555937]
Li X, Catalina F, Grundy SM, Patel S. Method to measure apolipoprotein B-48 and B-100 secretion rates in an individual mouse: evidence for a very rapid turnover of VLDL and preferential removal of B-48- relative to B-100-containing lipoproteins. J Lipid Res 1996; 37(1): 210-20.
[PMID: 8820116]
Breslow JL. Mouse models of atherosclerosis. Science 1996; 272(5262): 685-8.
[] [PMID: 8614828]
Powell-Braxton L, Véniant M, Latvala RD, et al. A mouse model of human familial hypercholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet. Nat Med 1998; 4(8): 934-8.
[] [PMID: 9701246]
Chiesa G, Johnson DF, Yao Z, et al. Expression of human apolipoprotein B100 in transgenic mice. Editing of human apolipoprotein B100 mRNA. J Biol Chem 1993; 268(32): 23747-50.
[PMID: 8226902]
Linton MF, Farese RV Jr, Chiesa G, et al. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). J Clin Invest 1993; 92(6): 3029-37.
[] [PMID: 8254057]
Purcell-Huynh DA, Farese RV Jr, Johnson DF, et al. Transgenic mice expressing high levels of human apolipoprotein B develop severe atherosclerotic lesions in response to a high-fat diet. J Clin Invest 1995; 95(5): 2246-57.
[] [PMID: 7738190]
Callow MJ, Stoltzfus LJ, Lawn RM, Rubin EM. Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice. Proc Natl Acad Sci USA 1994; 91(6): 2130-4.
[] [PMID: 8134359]
Bjelik A, Bereczki E, Gonda S, et al. Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis. Neurochem Int 2006; 49(4): 393-400.
[] [PMID: 16546298]
Huang LS, Voyiaziakis E, Markenson DF, Sokol KA, Hayek T, Breslow JL. apo B gene knockout in mice results in embryonic lethality in homozygotes and neural tube defects, male infertility, and reduced HDL cholesterol ester and apo A-I transport rates in heterozygotes. J Clin Invest 1995; 96(5): 2152-61.
[] [PMID: 7593600]
Farese RV Jr, Ruland SL, Flynn LM, Stokowski RP, Young SG. Knockout of the mouse apolipoprotein B gene results in embryonic lethality in homozygotes and protection against diet-induced hypercholesterolemia in heterozygotes. Proc Natl Acad Sci USA 1995; 92(5): 1774-8.
[] [PMID: 7878058]
Caramelli P, Nitrini R, Maranhão R, et al. Increased apolipoprotein B serum concentration in Alzheimer’s disease. Acta Neurol Scand 1999; 100(1): 61-3.
[] [PMID: 10416513]
Lénárt N, Szegedi V, Juhász G, et al. Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB-100 transgenic mice. PLoS One 2012; 7(9): e46007
[] [PMID: 23029362]
Hoyk Z, Tóth ME, Lénárt N, et al. Cerebrovascular pathology in hypertriglyceridemic APOB-100 transgenic mice. Front Cell Neurosci 2018; 12: 380.
[] [PMID: 30410436]
Csont T, Bereczki E, Bencsik P, et al. Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice. Cardiovasc Res 2007; 76(1): 100-9.
[] [PMID: 17658498]
Sanan DA, Newland DL, Tao R, et al. Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: no accentuation by apolipoprotein(a). Proc Natl Acad Sci USA 1998; 95(8): 4544-9.
[] [PMID: 9539774]
Grass DS, Saini U, Felkner RH, et al. Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normolipidemic humans. J Lipid Res 1995; 36(5): 1082-91.
[PMID: 7658156]
Collaboration PS.. Blood cholesterol and vascular mortality by age , sex , and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007; 370(9602): 1829-39.
Williams KJ, Tabas I. The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol 1995; 15(5): 551-61.
[] [PMID: 7749869]
Callow MJ, Verstuyft J, Tangirala R, Palinski W, Rubin EM. Atherogenesis in transgenic mice with human apolipoprotein B and lipoprotein (a). J Clin Invest 1995; 96(3): 1639-46.
[] [PMID: 7657833]
Hofman A, Ott A, Breteler MM, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997; 349(9046): 151-4.
[] [PMID: 9111537]
Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005; 62(10): 1556-60.
[] [PMID: 16216938]
Xu W, Qiu C, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study. Diabetes 2009; 58(1): 71-7.
[] [PMID: 18952836]
Laukka EJ, Fratiglioni L, Bäckman L. The influence of vascular disease on cognitive performance in the preclinical and early phases of Alzheimer’s disease. Dement Geriatr Cogn Disord 2010; 29(6): 498-503.
[] [PMID: 20523048]
Lathe R, Sapronova A, Kotelevtsev Y. Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr 2014; 14: 36.
[] [PMID: 24656052]
Santos CY, Snyder PJ, Wu W-C, Zhang M, Echeverria A, Alber J. Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis. Alzheimers Dement (Amst) 2017; 7: 69-87.
[] [PMID: 28275702]
Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37(1): 13-25.
[] [PMID: 19664713]
Fanning AS, Anderson JM. Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions. Ann N Y Acad Sci 2009; 1165: 113-20.
[] [PMID: 19538295]
Campos-Bedolla P, Walter FR, Veszelka S, Deli MA. Role of the blood-brain barrier in the nutrition of the central nervous system. Arch Med Res 2014; 45(8): 610-38.
[] [PMID: 25481827]
Blasiole DA, Davis RA, Attie AD. The physiological and molecular regulation of lipoprotein assembly and secretion. Mol Biosyst 2007; 3(9): 608-19.
[] [PMID: 17700861]
Brown MS, Kovanen PT, Goldstein JL. Regulation of plasma cholesterol by lipoprotein receptors. Science 1981; 212(4495): 628-35.
[] [PMID: 6261329]
Begley DJ. ABC transporters and the blood-brain barrier. Curr Pharm Des 2004; 10(12): 1295-312.
[] [PMID: 15134482]
Janzer RC, Raff MC. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 1987; 325(6101): 253-7.
[] [PMID: 3543687]
Estrada C, Bready JV, Berliner JA, Pardridge WM, Cancilla PA. Astrocyte growth stimulation by a soluble factor produced by cerebral endothelial cells in vitro. J Neuropathol Exp Neurol 1990; 49(6): 539-49.
[] [PMID: 2230835]
Kacem K, Lacombe P, Seylaz J, Bonvento G. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 1998; 23(1): 1-10.
[<1:AID-GLIA1>3.0.CO;2-B] [PMID: 9562180]
Willis CL, Leach L, Clarke GJ, Nolan CC, Ray DE. Reversible disruption of tight junction complexes in the rat blood-brain barrier, following transitory focal astrocyte loss. Glia 2004; 48(1): 1-13.
[] [PMID: 15326610]
Rash JE, Yasumura T, Hudson CS, Agre P, Nielsen S. Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. Proc Natl Acad Sci USA 1998; 95(20): 11981-6.
[] [PMID: 9751776]
Palazzo C, Buccoliero C, Mola MG, et al. AQP4ex is crucial for the anchoring of AQP4 at the astrocyte end-feet and for neuromyelitis optica antibody binding. Acta Neuropathol Commun 2019; 7(1): 51.
[] [PMID: 30935410]
Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP. Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 1997; 17(1): 171-80.
[] [PMID: 8987746]
Nehls V, Schuchardt E, Drenckhahn D. The effect of fibroblasts, vascular smooth muscle cells, and pericytes on sprout formation of endothelial cells in a fibrin gel angiogenesis system. Microvasc Res 1994; 48(3): 349-63.
[] [PMID: 7537351]
Arihiro S, Ohtani H, Hiwatashi N, Torii A, Sorsa T, Nagura H. Vascular smooth muscle cells and pericytes express MMP-1, MMP-9, TIMP-1 and type I procollagen in inflammatory bowel disease. Histopathology 2001; 39(1): 50-9.
[] [PMID: 11454044]
Nakaoke R, Verma S, Niwa M, et al. Glucose-regulated blood-brain barrier transport of insulin: pericyte-astrocyte-endothelial cell cross talk. Int J Neuroprot Neuroregener 2007; 3: 195-200.
Dore-Duffy P. Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 2008; 14(16): 1581-93.
[] [PMID: 18673199]
Kutcher ME, Herman IM. The pericyte: cellular regulator of microvascular blood flow. Microvasc Res 2009; 77(3): 235-46.
[] [PMID: 19323975]
Armulik A, Genové G, Mäe M, et al. Pericytes regulate the blood-brain barrier. Nature 2010; 468(7323): 557-61.
[] [PMID: 20944627]
Wang S, Voisin M-B, Larbi KY, et al. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med 2006; 203(6): 1519-32.
[] [PMID: 16754715]
Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 2011; 21(2): 193-215.
[] [PMID: 21839917]
Sagare AP, Bell RD, Zhao Z, et al. Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat Commun 2013; 4: 2932.
[] [PMID: 24336108]
Nakagomi T, Kubo S, Nakano-Doi A, et al. Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells. Stem Cells 2015; 33(6): 1962-74.
[] [PMID: 25694098]
Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010; 468(7323): 562-6.
[] [PMID: 20944625]
Banks WA, Kovac A, Morofuji Y. Neurovascular unit crosstalk: Pericytes and astrocytes modify cytokine secretion patterns of brain endothelial cells. J Cereb Blood Flow Metab 2018; 38(6): 1104-18.
[] [PMID: 29106322]
Rochfort KD, Cummins PM. The blood-brain barrier endothelium: a target for pro-inflammatory cytokines. Biochem Soc Trans 2015; 43(4): 702-6.
[] [PMID: 26551716]
Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 2018; 14(3): 133-50.
[] [PMID: 29377008]
Muñoz-Fernández MA, Fresno M. The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. Prog Neurobiol 1998; 56(3): 307-40.
[] [PMID: 9770242]
Incalza MA, D’Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol 2018; 100: 1-19.
[] [PMID: 28579545]
Dias HKI, Brown CLR, Polidori MC, Lip GY, Griffiths HR. LDL-lipids from patients with hypercholesterolaemia and Alzheimer’s disease are inflammatory to microvascular endothelial cells: mitigation by statin intervention. Clin Sci (Lond) 2015; 129(12): 1195-206.
[] [PMID: 26399707]
Park JH, Hong KS, Lee EJ, Lee J, Kim DE. High levels of apolipoprotein B/AI ratio are associated with intracranial atherosclerotic stenosis. Stroke 2011; 42(11): 3040-6.
[] [PMID: 21868729]
Turan TN, Makki AA, Tsappidi S, et al. WASID Investigators. Risk factors associated with severity and location of intracranial arterial stenosis. Stroke 2010; 41(8): 1636-40.
[] [PMID: 20616323]
Bowman GL, Kaye JA, Quinn JF. Dyslipidemia and blood-brain barrier integrity in Alzheimer’s disease. Curr Gerontol Geriatr Res 2012; 2012: 184042
[] [PMID: 22654903]
Chattopadhyay R, Dyukova E, Singh NK, Ohba M, Mobley JA, Rao GN. Vascular endothelial tight junctions and barrier function are disrupted by 15(S)-hydroxyeicosatetraenoic acid partly via protein kinase C ε-mediated zona occludens-1 phosphorylation at threonine 770/772. J Biol Chem 2014; 289(6): 3148-63.
[] [PMID: 24338688]
Eiselein L, Wilson DW, Lamé MW, Rutledge JC. Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis. Am J Physiol Heart Circ Physiol 2007; 292(6): H2745-53.
[] [PMID: 17259442]
Wang L, Sapuri-Butti AR, Aung HH, Parikh AN, Rutledge JC. Triglyceride-rich lipoprotein lipolysis increases aggregation of endothelial cell membrane microdomains and produces reactive oxygen species. Am J Physiol Heart Circ Physiol 2008; 295(1): H237-44.
[] [PMID: 18487440]
Antonios N, Angiolillo DJ, Silliman S. Hypertriglyceridemia and ischemic stroke. Eur Neurol 2008; 60(6): 269-78.
[] [PMID: 18824854]
Klafke JZ, Porto FG, Batista R, et al. Association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals. Clin Chim Acta 2015; 448: 50-7.
[] [PMID: 26115893]
Lee LL, Aung HH, Wilson DW, Anderson SE, Rutledge JC, Rutkowsky JM. Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress. Am J Physiol Cell Physiol 2017; 312(4): C500-16.
[] [PMID: 28077357]
Jais A, Solas M, Backes H, et al. Myeloid-cell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity. Cell 2016; 165(4): 882-95.
[] [PMID: 27133169]
Erickson MA, Dohi K, Banks WA. Neuroinflammation: a common pathway in CNS diseases as mediated at the blood-brain barrier. Neuroimmunomodulation 2012; 19(2): 121-30.
[] [PMID: 22248728]
Storck SE, Hartz AMS, Bernard J, et al. The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM. Brain Behav Immun 2018; 73: 21-33.
[] [PMID: 30041013]
Cirrito JR, Deane R, Fagan AM, et al. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J Clin Invest 2005; 115(11): 3285-90.
[] [PMID: 16239972]
Zechariah A, ElAli A, Hagemann N, et al. Hyperlipidemia attenuates vascular endothelial growth factor-induced angiogenesis, impairs cerebral blood flow, and disturbs stroke recovery via decreased pericyte coverage of brain endothelial cells. Arterioscler Thromb Vasc Biol 2013; 33(7): 1561-7.
[] [PMID: 23559636]
Hohsfield LA, Daschil N, Orädd G, Strömberg I, Humpel C. Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer’s disease mouse models. Mol Cell Neurosci 2014; 63: 83-95.
[] [PMID: 25447943]
Loera-Valencia R, Goikolea J, Parrado-Fernandez C, Merino-Serrais P, Maioli S. Alterations in cholesterol metabolism as a risk factor for developing Alzheimer’s disease: Potential novel targets for treatment. J Steroid Biochem Mol Biol 2019; 190: 104-14.
[] [PMID: 30878503]
Kuo YM, Emmerling MR, Bisgaier CL, et al. Elevated low-density lipoprotein in Alzheimer’s disease correlates with brain abeta 1-42 levels. Biochem Biophys Res Commun 1998; 252(3): 711-5.
[] [PMID: 9837771]
Wingo TS, Cutler DJ, Wingo AP, et al. Association of early-onset alzheimer disease with elevated low-density lipoprotein cholesterol levels and rare genetic coding variants of APOB. JAMA Neurol 2019; 76(7): 809-17.
[] [PMID: 31135820]
Williams VJ, Leritz EC, Shepel J, et al. Interindividual variation in serum cholesterol is associated with regional white matter tissue integrity in older adults. Hum Brain Mapp 2013; 34(8): 1826-41.
[] [PMID: 22438182]
Song F, Poljak A, Crawford J, et al. Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals. PLoS One 2012; 7(6)e34078
[] [PMID: 22701550]
Kawano M, Kawakami M, Otsuka M, Yashima H, Yaginuma T, Ueki A. Marked decrease of plasma apolipoprotein AI and AII in Japanese patients with late-onset non-familial Alzheimer’s disease. Clin Chim Acta 1995; 239(2): 209-11.
[] [PMID: 8542660]
Merched A, Xia Y, Visvikis S, Serot JM, Siest G. Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer’s disease. Neurobiol Aging 2000; 21(1): 27-30.
[] [PMID: 10794845]
Namba Y, Tsuchiya H, Ikeda K. Apolipoprotein B immunoreactivity in senile plaque and vascular amyloids and neurofibrillary tangles in the brains of patients with Alzheimer’s disease. Neurosci Lett 1992; 134(2): 264-6.
[] [PMID: 1375354]
Takechi R, Galloway S, Pallebage-Gamarallage M, Wellington C, Johnsen R, Mamo JC. Three-dimensional colocalization analysis of plasma-derived apolipoprotein B with amyloid plaques in APP/PS1 transgenic mice. Histochem Cell Biol 2009; 131(5): 661-6.
[] [PMID: 19225804]
Dodelet-Devillers A, Cayrol R, van Horssen J, et al. Functions of lipid raft membrane microdomains at the blood-brain barrier. J Mol Med (Berl) 2009; 87(8): 765-74.
[] [PMID: 19484210]
Lénárt N, Walter FR, Bocsik A, et al. Cultured cells of the blood-brain barrier from apolipoprotein B-100 transgenic mice: effects of oxidized low-density lipoprotein treatment. Fluids Barriers CNS 2015; 12: 17.
[] [PMID: 26184769]
Raffaitin C, Gin H, Empana J-P, et al. Metabolic syndrome and risk for incident Alzheimer’s disease or vascular dementia: the Three-City Study. Diabetes Care 2009; 32(1): 169-74.
[] [PMID: 18945929]
Nägga K, Gustavsson A-M, Stomrud E, et al. Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later. Neurology 2018; 90(1): e73-81.
[] [PMID: 29196581]
Burgess BL, McIsaac SA, Naus KE, et al. Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer’s disease mouse models with abundant A β in plasma. Neurobiol Dis 2006; 24(1): 114-27.
[] [PMID: 16899370]
Houlden H, Crook R, Hardy J, Roques P, Collinge J, Rossor M. Confirmation that familial clustering and age of onset in late onset Alzheimer’s disease are determined at the apolipoprotein E locus. Neurosci Lett 1994; 174(2): 222-4.
[] [PMID: 7970184]
Houlden H, Crook R, Duff K, et al. Apolipoprotein E alleles but neither apolipoprotein B nor apolipoprotein AI/CIII alleles are associated with late onset, familial Alzheimer’s disease. Neurosci Lett 1995; 188(3): 202-4.
[] [PMID: 7609909]
Li G, Bien-Ly N, Andrews-Zwilling Y, et al. GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice. Cell Stem Cell 2009; 5(6): 634-45.
[] [PMID: 19951691]
Koizumi K, Hattori Y, Ahn SJ, et al. Apoε4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function. Nat Commun 2018; 9(1): 3816.
[] [PMID: 30232327]
Tachibana M, Holm M-L, Liu C-C, et al. APOE4-mediated amyloid-β pathology depends on its neuronal receptor LRP1. J Clin Invest 2019; 129(3): 1272-7.
[] [PMID: 30741718]
Peng KY, Pérez-González R, Alldred MJ, et al. Apolipoprotein E4 genotype compromises brain exosome production. Brain 2019; 142(1): 163-75.
[] [PMID: 30496349]
Nuriel T, Peng KY, Ashok A, et al. The endosomal-lysosomal pathway is dysregulated by APOE4 expression in vivo. Front Neurosci 2017; 11: 702.
[] [PMID: 29311783]
Pullinger CR, Kane JP, Malloy MJ. Primary hypercholesterolemia: genetic causes and treatment of five monogenic disorders. Expert Rev Cardiovasc Ther 2003; 1(1): 107-19.
[] [PMID: 15030301]
Zambón D, Quintana M, Mata P, et al. Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Am J Med 2010; 123(3): 267-74.
[] [PMID: 20193836]
Elder GA, Ragnauth A, Dorr N, et al. Increased locomotor activity in mice lacking the low-density lipoprotein receptor. Behav Brain Res 2008; 191(2): 256-65.
[] [PMID: 18466986]
Moreira ELG, de Oliveira J, Nunes JC, et al. Age-related cognitive decline in hypercholesterolemic LDL receptor knockout mice (LDLr-/-): evidence of antioxidant imbalance and increased acetylcholinesterase activity in the prefrontal cortex. J Alzheimers Dis 2012; 32(2): 495-511.
[] [PMID: 22810096]
Wang SH, Huang Y, Yuan Y, Xia WQ, Wang P, Huang R. LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses. Lipids Health Dis 2014; 13: 175.
[] [PMID: 25413784]
de Oliveira J, Hort MA, Moreira ELG, et al. Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress. Neuroscience 2011; 197: 99-106.
[] [PMID: 21945034]
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011; 12(12): 723-38.
[] [PMID: 22048062]
Löffler T, Flunkert S, Havas D, et al. Impact of ApoB-100 expression on cognition and brain pathology in wild-type and hAPPsl mice. Neurobiol Aging 2013; 34(10): 2379-88.
[] [PMID: 23643485]
Süle Z, Mracskó E, Bereczki E, et al. Capillary injury in the ischemic brain of hyperlipidemic, apolipoprotein B-100 transgenic mice. Life Sci 2009; 84(25-26): 935-9.
[] [PMID: 19409916]
Wu Z, Guo H, Chow N, et al. Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nat Med 2005; 11(9): 959-65.
[] [PMID: 16116430]
Zhao Z, Zlokovic BV. Blood-brain barrier: a dual life of MFSD2A? Neuron 2014; 82(4): 728-30.
[] [PMID: 24853933]
Tomimoto H, Akiguchi I, Wakita H, Suenaga T, Nakamura S, Kimura J. Regressive changes of astroglia in white matter lesions in cerebrovascular disease and Alzheimer’s disease patients. Acta Neuropathol 1997; 94(2): 146-52.
[] [PMID: 9255389]
Bereczki E, Bernát G, Csont T, Ferdinandy P, Scheich H, Sántha M. Overexpression of human apolipoprotein B-100 induces severe neurodegeneration in transgenic mice. J Proteome Res 2008; 7(6): 2246-52.
[] [PMID: 18473452]

© 2024 Bentham Science Publishers | Privacy Policy