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

TitleDifferences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.
Publication TypeJournal Article
Year of Publication2006
AuthorsXu, 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
JournalNeurobiol Dis
Volume21
Issue2
Pagination256-75
Date Published2006 Feb
ISSN0969-9961
KeywordsAged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Female, Gene Expression, Genotype, Hippocampus, Humans, In Situ Hybridization, Male, Oligonucleotide Array Sequence Analysis, Risk Factors, Software, Transcription, Genetic
Abstract

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).

DOI10.1016/j.nbd.2005.07.004
Alternate JournalNeurobiol. Dis.
PubMed ID16198584
Grant ListAG05 128 / / Wellcome Trust / United Kingdom
AG11268 / AG / NIA NIH HHS / United States
AG13308 / AG / NIA NIH HHS / United States
AG19085 / AG / NIA NIH HHS / United States
AGIO123 / / PHS HHS / United States
MH52453 / MH / NIMH NIH HHS / United States
MH59528 / MH / NIMH NIH HHS / United States
NS031 153 / NS / NINDS NIH HHS / United States
NS3 9764 / NS / NINDS NIH HHS / United States
NS31 153 / NS / NINDS NIH HHS / United States