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ISSN (Print): 1874-6098
ISSN (Online): 1874-6128

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Review Article

Cholesterol and Dementia: A Long and Complicated Relationship

Author(s): Oliwia McFarlane* and Kornelia Kędziora-Kornatowska

Volume 13, Issue 1, 2020

Page: [42 - 51] Pages: 10

DOI: 10.2174/1874609812666190917155400

Abstract

Background: There is a huge demand for efficient strategies for maintaining cognitive wellbeing with age, especially in the context of population aging. Dementia constitutes the main reason for disability and dependency in the elderly. Identification of potential risk and protective factors, as well as determinants of conversion from MCI to dementia, is therefore crucial. In case of Alzheimer’s disease, the most prevalent dementia syndrome amongst the members of modern societies, neurodegenerative processes in the brain can begin many years before first clinical symptoms appear. First functional changes typically mean advanced neuron loss, therefore, the earliest possible diagnosis is critical for implementation of promising early pharmaceutical interventions.

Objective: The study aimed to discuss the relationships between both circulating and brain cholesterol with cognition, and explore its potential role in early diagnosis of cognitive disorders.

Methods: Literature review.

Results: The causal role of high cholesterol levels in AD or MCI has not been confirmed. It has been postulated that plasma levels of 24(S)-OHC can potentially be used as an early biochemical marker of altered cholesterol homeostasis in the CNS. Some studies brought conflicting results, finding normal or lowered levels of 24(S)-OHC in dementia patients compared to controls. In spite of decades of research on the relationship between cholesterol and dementia, so far, no single trusted indicator of an early cognitive deterioration has been identified.

Conclusion: The current state of knowledge makes the use of cholesterol markers of cognitive decline in clinical practice impossible

Keywords: Alzheimer’s disease, biomarker, cholesterol, cognition, dementia, mild cognitive impairment, 24(S)- hydroxycholesterol.

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Graphical Abstract

[1]
Alzheimer's Disease Facts and Figures, an annual report released by the Alzheimer's Association. Available at: https://www.alz.org/alzheimers-dementia/facts-figures (Accessed May 2019).
[2]
World Health Organization, Dementia Factsheet. Available at: https://www.who.int/news-room/fact-sheets/detail/dementia (Accessed May 2019).
[3]
Wimo A, Guerchet M, Ali GC, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement 2017; 13(1): 1-7.
[http://dx.doi.org/10.1016/j.jalz.2016.07.150] [PMID: 27583652]
[4]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed (DSM-5). Arlington, VA: American Psychiatric Publishing 2013.
[5]
World Health Organization. ICD-10 International Statistical Classification of Diseases and Related Health Problems 10. New York: World Health Organization 2008.
[6]
Chertkow H, Feldman HH, Jacova C, Massoud F. Definitions of dementia and predementia states in Alzheimer’s disease and vascular cognitive impairment: consensus from the Canadian conference on diagnosis of dementia. Alzheimers Res Ther 2013; 5(Suppl. 1): S2.
[http://dx.doi.org/10.1186/alzrt198] [PMID: 24565215]
[7]
Sheehan B. Assessment scales in dementia. Ther Adv Neurol Disorder 2012; 5(6): 349-58.
[http://dx.doi.org/10.1177/1756285612455733] [PMID: 23139705]
[8]
Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral and psychological symptoms of dementia. Front Neurol 2012; 3: 73.
[http://dx.doi.org/10.3389/fneur.2012.00073] [PMID: 22586419]
[9]
Chertkow H. Diagnosis and treatment of dementia: introduction. Introducing a series based on the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. CMAJ 2008; 178(3): 316-21.
[http://dx.doi.org/10.1503/cmaj.070795] [PMID: 18227452]
[10]
Arneson D, Zhang Y, Yang X, Narayanan M. Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks. J Genet 2018; 97(3): 795-806.
[http://dx.doi.org/10.1007/s12041-018-0963-3] [PMID: 30027910]
[11]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 2012; 8(2): 131-68.
[http://dx.doi.org/10.1016/j.jalz.2012.02.001] [PMID: 22404854]
[12]
Alzheimer Society of Canada. Lewy body dementia. Available at: www.alzheimer.ca/en/About-dementia/Dementias/Lewy-Body-Dementia (accessed May 2019).
[13]
Alzheimer Society of Canada. Front temporal dementia. Available at: www.alzheimer.ca/en/About-dementia/Dementias/Frontotemporal-Dementia-and-Pick-s-disease (Accessed May 2019).
[14]
Alzheimer Society of Canada. Vascular dementia. Available at: www.alzheimer.ca/en/About-dementia/Dementias/Vascular-Dementia (Accessed May 2019).
[15]
Wiederkehr S, Simard M, Fortin C, van Reekum R. Validity of the clinical diagnostic criteria for vascular dementia: a critical review. Part II. J Neuropsychiatry Clin Neurosci 2008; 20(2): 162-77.
[http://dx.doi.org/10.1176/jnp.2008.20.2.162] [PMID: 18451187]
[16]
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011; 12(12): 723-38.
[http://dx.doi.org/10.1038/nrn3114] [PMID: 22048062]
[17]
Kling MA, Trojanowski JQ, Wolk DA, Lee VM, Arnold SE. Vascular disease and dementias: paradigm shifts to drive research in new directions. Alzheimers Dement 2013; 9(1): 76-92.
[http://dx.doi.org/10.1016/j.jalz.2012.02.007] [PMID: 23183137]
[18]
Björkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 2004; 24(5): 806-15.
[http://dx.doi.org/10.1161/01.ATV.0000120374.59826.1b] [PMID: 14764421]
[19]
Chari D, Ali R, Gupta R. Reversible dementia in elderly: Really uncommon? J Geriatr Ment Health 2015; 2: 30-7.
[http://dx.doi.org/10.4103/2348-9995.161378]
[20]
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56(3): 303-8.
[http://dx.doi.org/10.1001/archneur.56.3.303] [PMID: 10190820]
[21]
Jack CR Jr, Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 257-62.
[http://dx.doi.org/10.1016/j.jalz.2011.03.004] [PMID: 21514247]
[22]
Auld DS, Kornecook TJ, Bastianetto S, Quirion R. Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 2002; 68(3): 209-45.
[http://dx.doi.org/10.1016/S0301-0082(02)00079-5] [PMID: 12450488]
[23]
Selkoe DJ. American College of Physicians. American Physiological Society. Alzheimer disease: mechanistic understanding predicts novel therapies. Ann Intern Med 2004; 140(8): 627-38.
[http://dx.doi.org/10.7326/0003-4819-140-8-200404200-00047] [PMID: 15096334]
[24]
Giaccone G, Arzberger T, Alafuzoff I, et al. New lexicon and criteria for the diagnosis of Alzheimer’s disease. Lancet Neurol 2011; 10(4): 298-9.
[http://dx.doi.org/10.1016/S1474-4422(11)70055-2] [PMID: 21435593]
[25]
Piaceri I, Nacmias B, Sorbi S. Genetics of familial and sporadic Alzheimer’s disease. Front Biosci (Elite Ed) 2013; 5(1): 167-77.
[http://dx.doi.org/10.2741/E605] [PMID: 23276979]
[26]
Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367(9): 795-804.
[http://dx.doi.org/10.1056/NEJMoa1202753] [PMID: 22784036]
[27]
Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 56(9): 1133-42.
[http://dx.doi.org/10.1212/WNL.56.9.1133] [PMID: 11342677]
[28]
Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2018; 90(3): 126-35.
[http://dx.doi.org/10.1212/WNL.0000000000004826] [PMID: 29282327]
[29]
Hildreth KL, Church S. Evaluation and management of the elderly patient presenting with cognitive complaints. Med Clin North Am 2015; 99(2): 311-35.
[http://dx.doi.org/10.1016/j.mcna.2014.11.006] [PMID: 25700586]
[30]
Gauthier S, Reisberg B, Zaudig M, et al. International Psychogeriatric Association Expert Conference on mild cognitive impairment. Mild cognitive impairment. Lancet 2006; 367(9518): 1262-70.
[http://dx.doi.org/10.1016/S0140-6736(06)68542-5] [PMID: 16631882]
[31]
Petrov AM, Kasimov MR, Zefirov AL. Brain cholesterol metabolism and its defects: Linkage to neurodegenerative diseases and synaptic dysfunction. Acta Naturae 2016; 8(1): 58-73.
[http://dx.doi.org/10.32607/20758251-2016-8-1-58-73] [PMID: 27099785]
[32]
Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T. Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem 2009; 78: 1017-40.
[http://dx.doi.org/10.1146/annurev.biochem.78.072407.103859] [PMID: 19489738]
[33]
Herz J, Bock HH. Lipoprotein receptors in the nervous system. Annu Rev Biochem 2002; 71: 405-34.
[http://dx.doi.org/10.1146/annurev.biochem.71.110601.135342] [PMID: 12045102]
[34]
Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000; 1: 507-37.
[http://dx.doi.org/10.1146/annurev.genom.1.1.507] [PMID: 11701639]
[35]
Sparks DL, Hunsaker JC III, Scheff SW, Kryscio RJ, Henson JL, Markesbery WR. Cortical senile plaques in coronary artery disease, aging and Alzheimer’s disease. Neurobiol Aging 1990; 11(6): 601-7.
[http://dx.doi.org/10.1016/0197-4580(90)90024-T] [PMID: 1704106]
[36]
Sparks DL, Scheff SW, Hunsaker JC III, Liu H, Landers T, Gross DR. Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol 1994; 126(1): 88-94.
[http://dx.doi.org/10.1006/exnr.1994.1044] [PMID: 8157129]
[37]
Anstey KJ, Ashby-Mitchell K, Peters R. Updating the evidence on the association between serum cholesterol and risk of late-life dementia: Review and meta-analysis. J Alzheimers Dis 2017; 56(1): 215-28.
[http://dx.doi.org/10.3233/JAD-160826] [PMID: 27911314]
[38]
Liu Q, An Y, Yu H, et al. Relationship between oxysterols and mild cognitive impairment in the elderly: a case-control study. Lipids Health Dis 2016; 15(1): 177.
[http://dx.doi.org/10.1186/s12944-016-0344-y] [PMID: 27724967]
[39]
Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000; 356(9242): 1627-31.
[http://dx.doi.org/10.1016/S0140-6736(00)03155-X] [PMID: 11089820]
[40]
Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000; 57(10): 1439-43.
[http://dx.doi.org/10.1001/archneur.57.10.1439] [PMID: 11030795]
[41]
Yaffe K, Barrett-Connor E, Lin F, Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol 2002; 59(3): 378-84.
[http://dx.doi.org/10.1001/archneur.59.3.378] [PMID: 11890840]
[42]
Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE. Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med 2007; 5: 20.
[http://dx.doi.org/10.1186/1741-7015-5-20] [PMID: 17640385]
[43]
Cramer C, Haan MN, Galea S, Langa KM, Kalbfleisch JD. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008; 71(5): 344-50.
[http://dx.doi.org/10.1212/01.wnl.0000319647.15752.7b] [PMID: 18663180]
[44]
Haag MD, Hofman A, Koudstaal PJ, Stricker BH, Breteler MM. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 2009; 80(1): 13-7.
[http://dx.doi.org/10.1136/jnnp.2008.150433] [PMID: 18931004]
[45]
Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA 1996; 275(1): 55-60.
[http://dx.doi.org/10.1001/jama.1996.03530250059028] [PMID: 8531288]
[46]
Vaughan CJ. Prevention of stroke and dementia with statins: Effects beyond lipid lowering. Am J Cardiol 2003; 91(4A): 23B-9B.
[http://dx.doi.org/10.1016/S0002-9149(02)03270-8] [PMID: 12615295]
[47]
Cucchiara B, Kasner SE. Use of statins in CNS disorders. J Neurol Sci 2001; 187(1-2): 81-9.
[http://dx.doi.org/10.1016/S0022-510X(01)00529-9] [PMID: 11440749]
[48]
Zhang X, Wen J, Zhang Z. Statins use and risk of dementia: A dose-response meta analysis. Medicine (Baltimore) 2018; 97(30): e11304
[http://dx.doi.org/10.1097/MD.0000000000011304] [PMID: 30045255]
[49]
Miida T, Takahashi A, Ikeuchi T. Prevention of stroke and dementia by statin therapy: experimental and clinical evidence of their pleiotropic effects. Pharmacol Ther 2007; 113(2): 378-93.
[http://dx.doi.org/10.1016/j.pharmthera.2006.09.003] [PMID: 17113151]
[50]
Bifulco M, Malfitano AM, Marasco G. Potential therapeutic role of statins in neurological disorders. Expert Rev Neurother 2008; 8(5): 827-37.
[http://dx.doi.org/10.1586/14737175.8.5.827] [PMID: 18457539]
[51]
Sierra S, Ramos MC, Molina P, Esteo C, Vázquez JA, Burgos JS. Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. J Alzheimers Dis 2011; 23(2): 307-18.
[http://dx.doi.org/10.3233/JAD-2010-101179] [PMID: 21098985]
[52]
Wanamaker BL, Swiger KJ, Blumenthal RS, Martin SS. Cholesterol, statins, and dementia: what the cardiologist should know. Clin Cardiol 2015; 38(4): 243-50.
[http://dx.doi.org/10.1002/clc.22361] [PMID: 25869997]
[53]
Pollen DA, Baker S, Hinerfeld D, et al. Prevention of Alzheimer’s disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein E ε 4. Alzheimers Res Ther 2010; 2(5): 31.
[http://dx.doi.org/10.1186/alzrt55] [PMID: 21062519]
[54]
Li G, Larson EB, Sonnen JA, et al. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology 2007; 69(9): 878-85.
[http://dx.doi.org/10.1212/01.wnl.0000277657.95487.1c] [PMID: 17724290]
[55]
Stroes E. Statins and LDL-cholesterol lowering: an overview. Curr Med Res Opin 2005; 21(Suppl. 6): S9-S16.
[http://dx.doi.org/10.1185/030079905X59102] [PMID: 16138936]
[56]
Chong PH, Seeger JD, Franklin C. Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med 2001; 111(5): 390-400.
[http://dx.doi.org/10.1016/S0002-9343(01)00870-1] [PMID: 11583643]
[57]
Schultz BG, Patten DK, Berlau DJ. The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Transl Neurodegener 2018; 7: 5.
[http://dx.doi.org/10.1186/s40035-018-0110-3] [PMID: 29507718]
[58]
Gu Q, Paulose-Ram R, Burt VL, Kit BK. Prescription cholesterollowering medication use in adults aged 40 and over: United States, 2003-2012. NCHS Data Brief 2014; 117(117): 1-8.
[PMID: 25536410]
[59]
Power MC, Weuve J, Sharrett AR, Blacker D, Gottesman RF. Statins, cognition, and dementia—systematic review and methodological commentary. Nat Rev Neurol 2015; 11(4): 220-9.
[http://dx.doi.org/10.1038/nrneurol.2015.35] [PMID: 25799928]
[60]
McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev 2016; 1: CD003160.
[PMID: 26727124]
[61]
Bunt CW, Hogan AJ. The effect of statins on dementia and cognitive decline. Am Fam Physician 2017; 95(3): 151-2.
[PMID: 28145677]
[62]
Friedhoff LT, Cullen EI, Geoghagen NS, Buxbaum JD. Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide. Int J Neuropsychopharmacol 2001; 4(2): 127-30.
[http://dx.doi.org/10.1017/S1461145701002310] [PMID: 11466161]
[63]
Romas SN, Tang MX, Berglund L, Mayeux R. APOE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 1999; 53(3): 517-21.
[http://dx.doi.org/10.1212/WNL.53.3.517] [PMID: 10449113]
[64]
Knittweis JW, McMullen WA. The effect of apoE on dementia is not through atherosclerosis: the Rotterdam study. Neurology 2000; 54(12): 2356-8.
[http://dx.doi.org/10.1212/WNL.54.12.2356-a] [PMID: 10881278]
[65]
Stewart R, White LR, Xue QL, Launer LJ. Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study. Arch Neurol 2007; 64(1): 103-7.
[http://dx.doi.org/10.1001/archneur.64.1.103] [PMID: 17210816]
[66]
Corti MC, Guralnik JM, Salive ME, et al. Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons. Ann Intern Med 1997; 126(10): 753-60.
[http://dx.doi.org/10.7326/0003-4819-126-10-199705150-00001] [PMID: 9148647]
[67]
Hu P, Seeman TE, Harris TB, Reuben DB. Does inflammation or undernutrition explain the low cholesterol-mortality association in high-functioning older persons? MacArthur studies of successful aging. J Am Geriatr Soc 2003; 51(1): 80-4.
[http://dx.doi.org/10.1034/j.1601-5215.2002.51014.x] [PMID: 12534850]
[68]
Chung HS, Lee JS, Kim JA, et al. Variability in total cholesterol concentration is associated with the risk of dementia: A nationwide population-based cohort study. Front Neurol 2019; 10: 441.
[http://dx.doi.org/10.3389/fneur.2019.00441] [PMID: 31133961]
[69]
Zandi PP, Sparks DL, Khachaturian AS, et al. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry 2005; 62(2): 217-24.
[http://dx.doi.org/10.1001/archpsyc.62.2.217] [PMID: 15699299]
[70]
Rea TD, Breitner JC, Psaty BM, et al. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol 2005; 62(7): 1047-51.
[http://dx.doi.org/10.1001/archneur.62.7.1047] [PMID: 16009757]
[71]
McGuinness B, O’Hare J, Craig D, Bullock R, Malouf R, Passmore P. Cochrane review on ‘Statins for the treatment of dementia’. Int J Geriatr Psychiatry 2013; 28(2): 119-26.
[http://dx.doi.org/10.1002/gps.3797] [PMID: 22473869]
[72]
McGuinness B, Craig D, Bullock R, Malouf R, Passmore P. Statins for the treatment of dementia. Cochrane Database Syst Rev 2014; 7(7): CD007514.
[PMID: 25004278]
[73]
Ledesma MD, Dotti CG. Amyloid excess in Alzheimer’s disease: what is cholesterol to be blamed for? FEBS Lett 2006; 580(23): 5525-32.
[http://dx.doi.org/10.1016/j.febslet.2006.06.038] [PMID: 16814780]
[74]
Wood WG, Li L, Müller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer’s disease: a debatable hypothesis. J Neurochem 2014; 129(4): 559-72.
[http://dx.doi.org/10.1111/jnc.12637] [PMID: 24329875]
[75]
Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 56(9): 1154-66.
[http://dx.doi.org/10.1212/WNL.56.9.1154] [PMID: 11342679]
[76]
Refolo LM, Malester B, LaFrancois J, et al. Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000; 7(4): 321-31.
[http://dx.doi.org/10.1006/nbdi.2000.0304] [PMID: 10964604]
[77]
Agrawal M, Biswas A. Molecular diagnostics of neurodegenerative disorders. Front Mol Biosci 2015; 2: 54.
[http://dx.doi.org/10.3389/fmolb.2015.00054] [PMID: 26442283]
[78]
Martín MG, Pfrieger F, Dotti CG. Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep 2014; 15(10): 1036-52.
[http://dx.doi.org/10.15252/embr.201439225] [PMID: 25223281]
[79]
Popp J, Lewczuk P, Kölsch H, et al. Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer’s disease. J Neurochem 2012; 123(2): 310-6.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07893.x] [PMID: 22845771]
[80]
Popp J, Meichsner S, Kölsch H, et al. Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer’s disease. Biochem Pharmacol 2013; 86(1): 37-42.
[http://dx.doi.org/10.1016/j.bcp.2012.12.007] [PMID: 23291240]
[81]
Dias IHK, Milic I, Lip GYH, Devitt A, Polidori MC, Griffiths HR. Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia. Redox Biol 2018; 16: 139-45.
[http://dx.doi.org/10.1016/j.redox.2018.02.014] [PMID: 29501047]
[82]
Testa G, Staurenghi E, Zerbinati C, et al. Changes in brain oxysterols at different stages of Alzheimer’s disease: Their involvement in neuroinflammation. Redox Biol 2016; 10: 24-33.
[http://dx.doi.org/10.1016/j.redox.2016.09.001] [PMID: 27687218]
[83]
Karasinska JM, Hayden MR. Cholesterol metabolism in Huntington disease. Nat Rev Neurol 2011; 7(10): 561-72.
[http://dx.doi.org/10.1038/nrneurol.2011.132] [PMID: 21894212]
[84]
Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J Biol Chem 1987; 262(29): 14352-60.
[PMID: 3115992]
[85]
Björkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 2006; 260(6): 493-508.
[http://dx.doi.org/10.1111/j.1365-2796.2006.01725.x] [PMID: 17116000]
[86]
Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL. Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 2005; 64(6): 1032-9.
[http://dx.doi.org/10.1212/01.WNL.0000154530.72969.11] [PMID: 15781822]
[87]
Schönknecht P, Lütjohann D, Pantel J, et al. Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer’s disease compared to healthy controls. Neurosci Lett 2002; 324(1): 83-5.
[http://dx.doi.org/10.1016/S0304-3940(02)00164-7] [PMID: 11983301]
[88]
Hughes TM, Rosano C, Evans RW, Kuller LH. Brain cholesterol metabolism, oxysterols, and dementia. J Alzheimers Dis 2013; 33(4): 891-911.
[http://dx.doi.org/10.3233/JAD-2012-121585] [PMID: 23076077]
[89]
Leoni V, Caccia C. 24S-hydroxycholesterol in plasma: a marker of cholesterol turnover in neurodegenerative diseases. Biochimie 2013; 95(3): 595-612.
[http://dx.doi.org/10.1016/j.biochi.2012.09.025] [PMID: 23041502]
[90]
Lütjohann D, Papassotiropoulos A, Björkhem I, et al. Plasma 24Shydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res 2000; 41(2): 195-8.
[PMID: 10681402]
[91]
Bretillon L, Sidén A, Wahlund LO, et al. Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci Lett 2000; 293(2): 87-90.
[http://dx.doi.org/10.1016/S0304-3940(00)01466-X] [PMID: 11027840]
[92]
Kölsch H, Heun R, Kerksiek A, Bergmann KV, Maier W, Lütjohann D. Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients. Neurosci Lett 2004; 368(3): 303-8.
[http://dx.doi.org/10.1016/j.neulet.2004.07.031] [PMID: 15364416]
[93]
Solomon A, Leoni V, Kivipelto M, et al. Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer’s disease. Neurosci Lett 2009; 462(1): 89-93.
[http://dx.doi.org/10.1016/j.neulet.2009.06.073] [PMID: 19560513]
[94]
Zuliani G, Donnorso MP, Bosi C, et al. Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer’s disease or vascular dementia: a case-control study. BMC Neurol 2011; 11: 121.
[http://dx.doi.org/10.1186/1471-2377-11-121] [PMID: 21970714]
[95]
de Chaves EP, Narayanaswami V. Apolipoprotein E and cholesterol in aging and disease in the brain. Future Lipidol 2008; 3(5): 505-30.
[http://dx.doi.org/10.2217/17460875.3.5.505] [PMID: 19649144]
[96]
Leoni V, Masterman T, Mousavi FS, et al. Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med 2004; 42(2): 186-91.
[http://dx.doi.org/10.1515/CCLM.2004.034] [PMID: 15061359]
[97]
Leoni V, Shafaati M, Salomon A, Kivipelto M, Björkhem I, Wahlund LO. Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment? Neurosci Lett 2006; 397(1-2): 83-7.
[http://dx.doi.org/10.1016/j.neulet.2005.11.046] [PMID: 16406316]
[98]
Leoni V, Masterman T, Patel P, Meaney S, Diczfalusy U, Björkhem I. Side chain oxidized oxysterols in cerebrospinal fluid and the integrity of blood-brain and blood-cerebrospinal fluid barriers. J Lipid Res 2003; 44(4): 793-9.
[http://dx.doi.org/10.1194/jlr.M200434-JLR200] [PMID: 12562838]
[99]
Papassotiropoulos A, Lütjohann D, Bagli M, et al. 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia. J Psychiatr Res 2002; 36(1): 27-32.
[http://dx.doi.org/10.1016/S0022-3956(01)00050-4] [PMID: 11755458]
[100]
Wang HL, Wang YY, Liu XG, et al. Cholesterol, 24-hydroxycholesterol, and 27-hydroxycholesterol as surrogate biomarkers in cerebrospinal fluid in mild cognitive impairment and alzheimer’s disease: A meta-analysis. J Alzheimers Dis 2016; 51(1): 45-55.
[http://dx.doi.org/10.3233/JAD-150734] [PMID: 26836015]
[101]
Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261(5123): 921-3.
[http://dx.doi.org/10.1126/science.8346443] [PMID: 8346443]
[102]
Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007; 39(1): 17-23.
[http://dx.doi.org/10.1038/ng1934] [PMID: 17192785]
[103]
Holly CH, Priyanka DP, Warren S, Vishnu S, Miranda NR. The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions. Neur Sig 2019; 3(2): NS20180203
[http://dx.doi.org/10.1042/NS20180203]
[104]
Rasmussen KL. Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review. Atherosclerosis 2016; 255: 145-55.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.10.037] [PMID: 28340945]
[105]
Michikawa M. Role of cholesterol in amyloid cascade: cholesterol-dependent modulation of tau phosphorylation and mitochondrial function. Acta Neurol Scand Suppl 2006; 185: 21-6.
[http://dx.doi.org/10.1111/j.1600-0404.2006.00681.x] [PMID: 16866907]
[106]
Shobab LA, Hsiung GY, Feldman HH. Cholesterol in Alzheimer’s disease. Lancet Neurol 2005; 4(12): 841-52.
[http://dx.doi.org/10.1016/S1474-4422(05)70248-9] [PMID: 16297842]
[107]
Poirier J. Apolipoprotein E represents a potent gene-based therapeutic target for the treatment of sporadic Alzheimer’s disease. Alzheimers Dement 2008; 4(1): S91-7.
[http://dx.doi.org/10.1016/j.jalz.2007.11.012] [PMID: 18632009]
[108]
Hirsch-Reinshagen V, Wellington CL. Cholesterol metabolism, apolipoprotein E, adenosine triphosphate-binding cassette transporters, and Alzheimer’s disease. Curr Opin Lipidol 2007; 18(3): 325-32.
[http://dx.doi.org/10.1097/MOL.0b013e32813aeabf] [PMID: 17495608]
[109]
Poirier J. Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer’s disease. Neurobiol Aging 2005; 26(3): 355-61.
[http://dx.doi.org/10.1016/j.neurobiolaging.2004.09.003] [PMID: 15639314]
[110]
Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci USA 2006; 103(15): 5644-51.
[http://dx.doi.org/10.1073/pnas.0600549103] [PMID: 16567625]
[111]
Mahley RW, Huang Y, Weisgraber KH. Detrimental effects of apolipoprotein E4: potential therapeutic targets in Alzheimer’s disease. Curr Alzheimer Res 2007; 4(5): 537-40.
[http://dx.doi.org/10.2174/156720507783018334] [PMID: 18220516]
[112]
Fenili D, McLaurin J. Cholesterol and apoe: a target for Alzheimer’s disease therapeutics. Curr Drug Targets CNS Neurol Disord 2005; 4(5): 553-67.
[http://dx.doi.org/10.2174/156800705774322085] [PMID: 16266288]
[113]
Pfrieger FW. Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? BioEssays 2003; 25(1): 72-8.
[http://dx.doi.org/10.1002/bies.10195] [PMID: 12508285]
[114]
Castellano JM, Kim J, Stewart FR, et al. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med 2011; 3(89): 89ra57
[http://dx.doi.org/10.1126/scitranslmed.3002156] [PMID: 21715678]
[115]
Leduc V, Jasmin-Bélanger S, Poirier J. APOE and cholesterol homeostasis in Alzheimer’s disease. Trends Mol Med 2010; 16(10): 469-77.
[http://dx.doi.org/10.1016/j.molmed.2010.07.008] [PMID: 20817608]
[116]
Lahiri DK. Apolipoprotein E as a target for developing new therapeutics for Alzheimer’s disease based on studies from protein, RNA, and regulatory region of the gene. J Mol Neurosci 2004; 23(3): 225-33.
[http://dx.doi.org/10.1385/JMN:23:3:225] [PMID: 15181251]
[117]
Hall K, Murrell J, Ogunniyi A, et al. Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba. Neurology 2006; 66(2): 223-7.
[http://dx.doi.org/10.1212/01.wnl.0000194507.39504.17] [PMID: 16434658]
[118]
Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet 2009; 374(9696): 1196-208.
[http://dx.doi.org/10.1016/S0140-6736(09)61460-4] [PMID: 19801098]
[119]
Humpel C, Hochstrasser T. Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease. World J Psychiatry 2011; 1(1): 8-18.
[http://dx.doi.org/10.5498/wjp.v1.i1.8] [PMID: 24175162]

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