The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

INTRODUCTION The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population. METHODS In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE e4 were analyzed across groups. RESULTS The prevalence of the APOE e4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE e4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001). DISCUSSION APOE e4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.