Significantly higher APOE abundance in the hippocampus of male alcoholics than male non-alcoholics

Objectives To explore the potential contribution of alcoholism to Alzheimer’s development at gene expression level, focusing on the mRNA levels of amyloid precursor protein (APP), presenilin 1 (PSEN1), apolipoprotein E (APOE), and tau protein

Methods A dataset from GEO (gene expression omnibus) of NCBI was selected, including 6 female age-matched alcoholism and controls, 14 male alcoholism and 13 male age-matched controls. All mRNA samples were from frozen human post-mortem hippocampus. The total 39 chips of affymetrix human gene 1.0 ST array were normalized by Robust Multichip Average (RMA), software. The abundance of mRNA was expressed at log2 scale. The comparison between groups was performed by Student’s t-test.

Results The APOE abundances in male alcoholic and non-alcoholic groups were 9.40//0.06 (mean//variance) and 9.12//0.11, p<0.01. The APOE abundances in female alcoholic and non-alcoholic groups were 8.80//0.08 and 9.11//0.21, no significant. The PSEN1 abundance in male alcoholic and non-alcoholic groups were 8.33//0.05 and 0.84//0.06, p<0.01. The PSEN1 abundance in female alcoholic and non-alcoholic groups were 8.45//0.25 and 8.97//0.04, no significant. The difference of PSEN1 abundances in combined alcoholic and control groups was significant, p<0.01). The APP and Tau did not have significant difference between groups. The difference of APOE between male and female alcoholics was significant, P(T<=t) two-tail: 0.004<0.05. But the difference of APOE between male and female non-alcoholics was not significant.

Conclusions Our explorative analysis in a small alcoholic population showed that there was a sex difference in APOE expression in alcoholism, suggesting that male alcoholics could have high risk to develop Alzheimer’s disease, particularly lower PSEN1 abundance in alcoholics than non-alcoholics. Validation in a larger volume is guaranteed.

Research Support T32EB006351