Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.

Journal Article (Journal Article)

Apolipoprotein E4 (APOE4) allele is a major risk factor for late-onset familial and sporadic Alzheimer disease (AD). The mechanism of action of APOE in the etiology of AD remains unclear. Using gene expression (microarray) analysis of human hippocampus from APOE3/3 AD and APOE4/4 AD cases, we found different gene transcription patterns between APOE4/4 and APOE3/3 AD cases. The expression of APOE4/4 alleles, in comparison to APOE3/3, is associated with upregulation of multiple gene transcripts encoding cell growth suppresser or arrest, signal transduction, myelinogenesis, cell adhesion and migration, heavy metal metabolism and detoxification. Whereas the APOE4 gene expression is associated with downregulation of gene transcripts involved in mitochondrial oxidative phosphorylation and energy metabolism, synaptic vesicle docking and fusing, and synaptic plasticity compared to APOE3. These mechanisms may contribute increased risk for AD and for cognitive dysfunction in AD patients who carry the APOE4 allele(s).

Full Text

Duke Authors

Cited Authors

  • Xu, P-T; Li, Y-J; Qin, X-J; Scherzer, CR; Xu, H; Schmechel, DE; Hulette, CM; Ervin, J; Gullans, SR; Haines, J; Pericak-Vance, MA; Gilbert, JR

Published Date

  • February 2006

Published In

Volume / Issue

  • 21 / 2

Start / End Page

  • 256 - 275

PubMed ID

  • 16198584

International Standard Serial Number (ISSN)

  • 0969-9961

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2005.07.004


  • eng

Conference Location

  • United States