A Quarter Century of APOE and Alzheimer's Disease: Progress to Date and the Path Forward

Neuron. 2019 Mar 6;101(5):820-838. doi: 10.1016/j.neuron.2019.01.056.

Abstract

Alzheimer's disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi "monogenic" role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative disorders. This review, based mostly on data from human studies, ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex. The authors also address one of the most fundamental question pertaining to APOE4 and AD: does APOE4 increase AD risk via a loss or gain of function? The answer will be of the utmost importance in guiding future research in AD.

Keywords: AD; APOE; ASO; Alzheimer’s disease; Apolipoprotein E; anti-sense oligonucleotide; cardiovascular disease; ethnicity; evolutionary genetics; gene-based therapy; neurodegenerative disease; pleiotropy; sex.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Animals
  • Apolipoprotein E4 / chemistry
  • Apolipoprotein E4 / genetics*
  • Apolipoprotein E4 / metabolism
  • Humans

Substances

  • Apolipoprotein E4