Mechanisms of sex differences in Alzheimer's disease

Neuron. 2024 Apr 17;112(8):1208-1221. doi: 10.1016/j.neuron.2024.01.024. Epub 2024 Feb 22.

Abstract

Alzheimer's disease (AD) and the mechanisms underlying its etiology and progression are complex and multifactorial. The higher AD risk in women may serve as a clue to better understand these complicated processes. In this review, we examine aspects of AD that demonstrate sex-dependent effects and delve into the potential biological mechanisms responsible, compiling findings from advanced technologies such as single-cell RNA sequencing, metabolomics, and multi-omics analyses. We review evidence that sex hormones and sex chromosomes interact with various disease mechanisms during aging, encompassing inflammation, metabolism, and autophagy, leading to unique characteristics in disease progression between men and women.

Keywords: Alzheimer’s disease; autophagy; estrogen; inflammation; metabolism; metabolomics; microbiome; microglia; sex differences.

Publication types

  • Review

MeSH terms

  • Aging
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Female
  • Humans
  • Inflammation / complications
  • Male
  • Risk Factors
  • Sex Characteristics