title: Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease.
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.
authors: 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.
authors: Judes
authors: J
authors: Poirier
authors: 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.
authors: Justin
authors: J
authors: Miron
authors: 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.
authors: Cynthia
authors: C
authors: Picard
authors: 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.
authors: Patrick
authors: P
authors: Gormley
authors: 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.
authors: Louise
authors: L
authors: Théroux
authors: 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.
authors: John
authors: J
authors: Breitner
authors: 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.
authors: Doris
authors: D
authors: Dea
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid / Q000172:deficiency* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D011341:Probucol
keywords: Alzheimer's disease; Apolipoprotein E; Cholesterol; Genetics; Lipids; Probucol; Statins