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).
