The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease. Issue 12 (3rd September 2020) - Jia, Longfei
Abstract: 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 ε4 were analyzed across groups. Results: The prevalence of the APOE ε4 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 ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57–5.45, P < .001). Discussion: APOE ε4 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.