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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Anticholesteremic Agents / pharmacology*
  • Anticholesteremic Agents / therapeutic use*
  • Apolipoprotein E4 / genetics*
  • Apolipoproteins E / cerebrospinal fluid
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / metabolism*
  • Brain / metabolism*
  • Female
  • Genetic Association Studies
  • Homeostasis*
  • Humans
  • Lipid Metabolism*
  • Male
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation / drug effects
  • Probucol / pharmacology*
  • Probucol / therapeutic use*
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Anticholesteremic Agents
  • Apolipoprotein E4
  • Apolipoproteins E
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Probucol