Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 Levels in Alzheimer’s: The Relation Between Neuroinflammatory Pathway and Severity of Dementia

Author(s): Nazrin Gulmammadli, Dildar Konukoğlu, Eda Merve Kurtuluş*, Didem Tezen, Muhammed Ibrahim Erbay and Melda Bozluolçay

Volume 19, Issue 12, 2022

Published on: 05 January, 2023

Page: [841 - 848] Pages: 8

DOI: 10.2174/1567205020666221226140721

Price: $65

Abstract

Alzheimer's disease (AD), which affects the world's aging population, is a progressive neurodegenerative disease requiring markers or tools to accurately and easily diagnose and monitor the process.

Objective: In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukin-6 (IL-6), Amyloid βeta-42 (Aβ- 42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation.

Methods: Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n = 21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, and p-tau181 levels.

Results: Levels of serum Aβ-42, SIRT1, HMGB1, and IL-6 were significantly higher (p< 0.001, p< 0.01, p< 0.001, and p< 0.001, respectively), and TLR4 levels were significantly lower (p< 0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels.

Conclusion: Our results show that the levels of the Aβ42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.

Keywords: Sirtuin-1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, p-tau181, dementia.

« Previous
[1]
van der Kant R, Goldstein LSB, Ossenkoppele R. Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci 2020; 21(1): 21-35.
[http://dx.doi.org/10.1038/s41583-019-0240-3] [PMID: 31780819]
[2]
Castellani RJ, Peclovits A, Perry G. Neuropathology of Alzheimer’s disease. In: pathobiology of human disease. Elsevier 2014; pp. 2014-.
[http://dx.doi.org/10.1016/B978-0-12-386456-7.04604-9]
[3]
Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 2020; 19(5): 422-33.
[http://dx.doi.org/10.1016/S1474-4422(20)30071-5] [PMID: 32333900]
[4]
Lalla R, Donmez G. The role of sirtuins in Alzheimer’s disease. Front Aging Neurosci 2013; 5: 16.
[http://dx.doi.org/10.3389/fnagi.2013.00016] [PMID: 23576985]
[5]
Balaiya S, Abu-Amero KK, Kondkar AA, Chalam KV. Sirtuins expression and their role in retinal diseases. Oxid Med Cell Longev 2017; 2017: 3187594.
[http://dx.doi.org/10.1155/2017/3187594] [PMID: 28197299]
[6]
Kilic U, Elibol B, Uysal O, et al. Specific alterations in the circulating levels of the SIRT1, TLR4, and IL7 proteins in patients with dementia. Exp Gerontol 2018; 111: 203-9.
[http://dx.doi.org/10.1016/j.exger.2018.07.018] [PMID: 30071285]
[7]
Paudel YN, Shaikh MF, Chakraborti A, et al. HMGB1: A common biomarker and potential target for TBI, neuroinflammation, epilepsy, and cognitive dysfunction. Front Neurosci 2018; 12: 628.
[http://dx.doi.org/10.3389/fnins.2018.00628] [PMID: 30271319]
[8]
Kiiski H, Långsjö J, Tenhunen J, et al. Time-courses of plasma IL-6 and HMGB-1 reflect initial severity of clinical presentation but do not predict poor neurologic outcome following subarachnoid hemorrhage. eNeurologicalSci 2017; 6: 55-62.
[http://dx.doi.org/10.1016/j.ensci.2016.11.010] [PMID: 29260012]
[9]
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS–ADRDA criteria. Lancet Neurol 2007; 6(8): 734-46.
[http://dx.doi.org/10.1016/S1474-4422(07)70178-3] [PMID: 17616482]
[10]
Singh V, Ubaid S. Role of Silent Information Regulator 1 (SIRT1) in regulating oxidative stress and inflammation. Inflammation 2020; 43(5): 1589-98.
[http://dx.doi.org/10.1007/s10753-020-01242-9] [PMID: 32410071]
[11]
Kumar R, Chaterjee P, Sharma PK, et al. Sirtuin1: A promising serum protein marker for early detection of Alzheimer’s disease. PLoS One 2013; 8(4): e61560.
[http://dx.doi.org/10.1371/journal.pone.0061560] [PMID: 23613875]
[12]
Pradhan R, Singh AK, Kumar P, et al. Blood circulatory level of seven sirtuins in alzheimer’s disease: Potent biomarker based on translational research. Mol Neurobiol 2022; 59(3): 1440-51.
[http://dx.doi.org/10.1007/s12035-021-02671-9] [PMID: 34993847]
[13]
Sinem F, Dildar K, Gökhan E, Melda B, Orhan Y, Filiz M. The serum protein and lipid oxidation marker levels in Alzheimer’s disease and effects of cholinesterase inhibitors and antipsychotic drugs therapy. Curr Alzheimer Res 2010; 7(5): 463-9.
[http://dx.doi.org/10.2174/156720510791383822] [PMID: 20043811]
[14]
Tang Y, Zhao X, Antoine D, et al. Regulation of posttranslational modifications of HMGB1 during immune responses. Antioxid Redox Signal 2016; 24(12): 620-34.
[http://dx.doi.org/10.1089/ars.2015.6409] [PMID: 26715031]
[15]
Festoff BW, Sajja RK, van Dreden P, Cucullo L. HMGB1 and thrombin mediate the blood-brain barrier dysfunction acting as biomarkers of neuroinflammation and progression to neurodegeneration in Alzheimer’s disease. J Neuroinflammation 2016; 13(1): 194.
[http://dx.doi.org/10.1186/s12974-016-0670-z] [PMID: 27553758]
[16]
Bowie A, O’Neill LAJ. The interleukin-1 receptor/Toll-like receptor superfamily: Signal generators for pro-inflammatory interleukins and microbial products. J Leukoc Biol 2000; 67(4): 508-14.
[http://dx.doi.org/10.1002/jlb.67.4.508] [PMID: 10770283]
[17]
Lewis H, Beher D, Cookson N, Oakley A, Piggott M, Morris CM. Quantification of Alzheimer pathology in aging and dementia: Age-related accumulation of amyloid-β(42) peptide in vascular dementia. Neuropathol Appl Neurobiol 2006; 32(2): 103-8.
[18]
Mayeux R, Honig LS, Tang MX, et al. Plasma A 40 and A 42 and Alzheimer’s disease: Relation to age, mortality, and risk. Neurology 2003; 61(9): 1185-90.
[http://dx.doi.org/10.1212/01.WNL.0000091890.32140.8F] [PMID: 14610118]
[19]
Udan ML, Ajit D, Crouse NR, Nichols MR. Toll-like receptors 2 and 4 mediate Abeta(1-42) activation of the innate immune response in a human monocytic cell line. J Neurochem 2008; 104(2): 524-33.
[http://dx.doi.org/10.1111/j.1471-4159.2007.05001.x] [PMID: 17986235]
[20]
Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K. Role of toll-like receptor signalling in A uptake and clearance. Brain 2006; 129(11): 3006-19.
[http://dx.doi.org/10.1093/brain/awl249] [PMID: 16984903]
[21]
Belkhelfa M, Beder N, Mouhoub D, et al. The involvement of neuroinflammation and necroptosis in the hippocampus during vascular dementia. J Neuroimmunol 2018; 320: 48-57.
[http://dx.doi.org/10.1016/j.jneuroim.2018.04.004] [PMID: 29759140]
[22]
Terai K, Matsuo A, McGeer PL. Enhancement of immunoreactivity for NF-κB in the hippocampal formation and cerebral cortex of Alzheimer’s disease. Brain Res 1996; 735(1): 159-68.
[http://dx.doi.org/10.1016/0006-8993(96)00310-1] [PMID: 8905182]
[23]
Kaltschmidt B, Ndiaye D, Korte M, et al. NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A/CREB signaling. Mol Cell Biol 2006; 26(8): 2936-46.
[http://dx.doi.org/10.1128/MCB.26.8.2936-2946.2006] [PMID: 16581769]
[24]
Lian H, Yang L, Cole A, et al. NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer’s disease. Neuron 2015; 85(1): 101-15.
[http://dx.doi.org/10.1016/j.neuron.2014.11.018] [PMID: 25533482]
[25]
García-García VA, Alameda JP, Page A, Casanova ML. Role of nf-κb in aging and age-related diseases: Lessons from genetically modified mouse models. Cells 2021; 10(8): 1906.
[http://dx.doi.org/10.3390/cells10081906] [PMID: 34440675]
[26]
Yang Y, Han C, Guo L, Guan Q. High expression of the HMGB1-TLR4 axis and its downstream signaling factors in patients with Parkinson’s disease and the relationship of pathological staging. Brain Behav 2018; 8(4): e00948.
[http://dx.doi.org/10.1002/brb3.948] [PMID: 29670828]
[27]
Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology 2021; 190: 108352.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108352] [PMID: 33035532]
[28]
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 2014; 69 (Suppl. 1): S4-9.
[http://dx.doi.org/10.1093/gerona/glu057] [PMID: 24833586]
[29]
Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 2012; 8(9): 1254-66.
[http://dx.doi.org/10.7150/ijbs.4679] [PMID: 23136554]
[30]
Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 2010; 68(10): 930-41.
[http://dx.doi.org/10.1016/j.biopsych.2010.06.012] [PMID: 20692646]
[31]
Bozluolcay M, Andican G, Fırtına S, Erkol G, Konukoglu D. Inflammatory hypothesis as a link between Alzheimer’s disease and diabetes mellitus. Geriatr Gerontol Int 2016; 16(10): 1161-6.
[http://dx.doi.org/10.1111/ggi.12602] [PMID: 26337250]
[32]
Uslu S, Eken Z, Demet A. Levels of amyloid beta-42, interleukin-6 and tumor necrosis factor-alpha in Alzheimer’s disease and vascular dementia. Neurochem Res 2012; 37(7): 1554-9.
[33]
Vishnu VY, Modi M, Garg VK, Mohanty M, Goyal MK, Lal V. Role of inflammatory and hemostatic biomarkers in Alzheimer’s and vascular dementia – A pilot study from a tertiary center in Northern India. Asian J Psychiatr 2016; 2017(29): 59-62.
[34]
Karadaş Ö, Koç G, Özön AÖ, Öztürk B, Konukoğlu D. Biomarkers of Alzheimer’s disease and vascular dementia simultaneously sampled from serum and cerebrospinal fluid. Turk Geriatri Derg 2017; 20(1): 1-7.
[35]
Sun YX, Minthon L, Wallmark A, Warkentin S, Blennow K, Janciauskiene S. Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 2003; 16(3): 136-44.
[http://dx.doi.org/10.1159/000071001] [PMID: 12826739]
[36]
Angelopoulos P, Agouridaki H, Vaiopoulos H, et al. Cytokines in Alzheimer’s disease and vascular dementia. Int J Neurosci 2008; 118(12): 1659-72.
[http://dx.doi.org/10.1080/00207450701392068] [PMID: 18937113]
[37]
Tang L, Chen Q, Meng Z, et al. Suppression of sirtuin-1 increases IL-6 expression by activation of the akt pathway during allergic asthma. Cell Physiol Biochem 2017; 43(5): 1950-60.
[http://dx.doi.org/10.1159/000484119] [PMID: 29055943]
[38]
Nelson PT, Jicha GA, Schmitt FA, et al. Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: Neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol 2007; 66(12): 1136-46.
[http://dx.doi.org/10.1097/nen.0b013e31815c5efb] [PMID: 18090922]
[39]
Tsai CL, Liang CS, Lee JT, et al. Associations between plasma biomarkers and cognition in patients with Alzheimer’s disease and amnestic mild cognitive impairment: A cross- sectional and longitudinal study. J Clin Med 2019; 8(11): 1893.
[http://dx.doi.org/10.3390/jcm8111893] [PMID: 31698867]
[40]
Chen SD, Huang YY, Shen XN, et al. Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer’s disease. Transl Psychiatry 2021; 11(1): 356.
[http://dx.doi.org/10.1038/s41398-021-01476-7] [PMID: 34120152]

Rights & Permissions Print Cite
Article Metrics
35
3
© 2024 Bentham Science Publishers | Privacy Policy