Project description:APOE4 allele is a major risk factor for late-onset Alzheimer disease (AD). The mechanism of action of APOE in AD remains unclear. To study the effects of APOE alleles on gene expression in AD, we have analyzed the gene transcription patterns of human hippocampus from APOE3/3, APOE3/4, APOE4/4 AD patients and normal control using Serial Analysis of Gene Expression (SAGE). Using SAGE, we found gene expression patterns in hippocampus of APOE3/4 and APOE4/4 AD patients differ substantially from those of APOE3/3 AD patients. APOE3/4 and APOE4/4 allele expression may activate similar genes or gene pools with associated functions. APOE4 AD alleles activate multiple tumor suppressors, tumor inducers and negative regulator of cell growth or repressors that may lead to increased cell arrest, senescent and apoptosis. In contrast, there is decreased expression of large clusters of genes associated with synaptic plasticity, synaptic vesicle trafficking (metabolism) and axonal/neuronal outgrowth. In addition, reduction of neurotransmitter receptors and Ca++ homeostasis, disruption of multiple signal transduction pathways, and loss of cell protection and notably mitochondrial oxidative phosphorylation/energy metabolism are associated with APOE3/4 and APOE4/4 AD alleles. These findings help define the mechanisms that APOE4 contribute increased risk for AD and identify new candidate genes conferring susceptibility to AD. Keywords: Serial Analysis of Gene Expression (SAGE); Apolipoprotein E (APOE3/3, APOE3/4, APOE4/4); Alzheimer disease; Hippocampus; apoptosis; signal pathways

2007-01-13 | GSE6677 | GEO

Conformational analysis of apolipoprotein E3/E4 heteromerization.

Project description: Not available

| S-EPMC6733585 | biostudies-literature

Apolipoprotein E4 genotype compromises brain exosome production.

Project description: Not available

| S-EPMC6308312 | biostudies-literature

A SAGE study of apolipoprotein E3/3, E3/4 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.

Project description: Not available

| S-EPMC3625967 | biostudies-literature

Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan.

Project description: Not available