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

Alzheimers Dement. 2020 Dec;16(12):1613-1623. doi: 10.1002/alz.12153. Epub 2020 Sep 3.

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.

Keywords: APOE; Alzheimer's disease; dementia; gene mutation; genetic risk effect; prevalence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / classification
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics*
  • China
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Risk Factors

Substances

  • Apolipoprotein E4