Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease.
Title | Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Poirier J, Miron J, Picard C, Gormley P, Théroux L, Breitner JCS, Dea D |
Journal | Neurobiol Aging |
Volume | 35 Suppl 2 |
Pagination | S3-10 |
Date Published | 2014 Sep |
ISSN | 1558-1497 |
Keywords | Alleles, Alzheimer Disease, Amyloid beta-Peptides, Anticholesteremic Agents, Apolipoprotein E4, Apolipoproteins E, Brain, Female, Genetic Association Studies, Homeostasis, Humans, Lipid Metabolism, Male, Peptide Fragments, Phosphorylation, Probucol, tau Proteins |
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. |
DOI | 10.1016/j.neurobiolaging.2014.03.037 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 24973118 |
Grant List | MOP-199321 / / Canadian Institutes of Health Research / Canada |