Current Atherosclerosis Reports

, 15:307

Dyslipidemia and the Risk of Alzheimer’s Disease

Coronary Heart Disease (JA Farmer, Section Editor)

DOI: 10.1007/s11883-012-0307-3

Cite this article as:
Reitz, C. Curr Atheroscler Rep (2013) 15: 307. doi:10.1007/s11883-012-0307-3
Part of the following topical collections:
  1. Topical Collection on Coronary Heart Disease


Whether cholesterol is implicated in the pathogenesis of Alzheimer’s disease (AD) is still controversial. Several studies that explored the association between lipids and/or lipid-lowering treatment and AD indicate a harmful effect of dyslipidemia on AD risk. The findings are supported by genetic linkage and association studies that have clearly identified several genes involved in cholesterol metabolism or transport as AD susceptibility genes, including apolipoprotein E (APOE), apolipoprotein J (APOJ, CLU), ATP-binding cassette subfamily A member 7(ABCA7), and sortilin-related receptor (SORL1). Functional cell biology studies further support a critical involvement of lipid raft cholesterol in the modulation of Aβ precursor protein processing by β-secretase and γ-secretase resulting in altered Aβ production. However, conflicting evidence comes from epidemiological studies showing no or controversial association between dyslipidemia and AD risk, randomized clinical trials observing no beneficial effect of statin therapy, and cell biology studies suggesting that there is little exchange between circulating and brain cholesterol, that increased membrane cholesterol level is protective by inhibiting loss of membrane integrity through amyloid cytotoxicity, and that cellular cholesterol inhibits colocalization of β-secretase 1 and Aβ precursor protein in nonraft membrane domains, thereby increasing generation of plasmin, an Aβ-degrading enzyme. The aim of this article is to provide a comprehensive review of the findings of epidemiological, genetic, and cell biology studies aiming to elucidate the role of cholesterol in the pathogenesis of AD.


Alzheimer's diseaseCholesterolHigh-density lipoproteinAβ peptidesAβ precursor proteinNeurodegenerationAmyloid

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.The Gertrude H. Sergievsky, the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and the Department of NeurologyColumbia University College of Physicians and SurgeonsNew YorkUSA
  2. 2.Gertrude H. Sergievsky CenterColumbia UniversityNew YorkUSA