Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:35

Review

Poirier, Judes^1,2,3  Miron, Justin^1,2,3  Picard, Cynthia^1,2,3  Gormley, Patrick^1,2,3  Theroux, Louise^1,2,3  Breitner, John^1,2,3  Dea, Doris^1,2,3 

[1] Ctr Studies Prevent Alzheimers Dis, Verdun, PQ, Canada

[2] Douglas Mental Hlth Univ Inst, Res Ctr, Mol Neurobiol Unit, Verdun, PQ, Canada

[3] McGill Univ, Dept Psychiat, Montreal, PQ, Canada

关键词: Alzheimer's disease;    Apolipoprotein E;    Cholesterol;    Lipids;    Probucol;    Statins;    Genetics;   

DOI  :  10.1016/j.neurobiolaging.2014.03.037

来源: Elsevier

【 摘 要 】

The discovery that the apolipoprotein E (apoE) epsilon 4 allele is genetically linked to both sporadic and familial late-onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid transport system could seriously affect lipid homeostasis in the brain of AD subjects. The presence of the e4 allele has been associated with lower levels of apoE in both serum and brain tissues of normal and AD subjects. In an attempt to reverse the apoE deficit in AD, we identified and characterized several apoE inducer agents using a low-throughput in vitro screening assay. The most promising of these compounds is called probucol. Administration of probucol, an old cholesterol-lowering drug, in a pilot trial in mild-to-moderate sporadic AD led to a significant increase in cerebrospinal fluid (CSF) apoE levels and a decrease in CSF in both phosphorylated tau 181 and beta-amyloid 1-42 concentrations without significant modifications of lipid hydroperoxide levels. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

Free