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Neurobiol Aging. 2014 Sep;35 Suppl 2:S3-10. doi: 10.1016/j.neurobiolaging.2014.03.037. Epub 2014 May 15.

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

Author information

1
Centre for Studies on the Prevention of Alzheimer's disease, Verdun, Quebec, Canada; Molecular Neurobiology Unit, Douglas Mental Health University Institute, Research Centre, Verdun, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada. Electronic address: judes.poirier@mcgill.ca.
2
Centre for Studies on the Prevention of Alzheimer's disease, Verdun, Quebec, Canada; Molecular Neurobiology Unit, Douglas Mental Health University Institute, Research Centre, Verdun, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Abstract

The discovery that the apolipoprotein E (apoE) ε4 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 ε4 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.

KEYWORDS:

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

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

statement All authors declare no conflicts. Written informed consent was obtained from all participants involved in the different studies discussed in this review. Approvals for the different studies were obtained from the Douglas Mental Health Institute Human Research Ethic Committee.

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