Stress regulates Alzheimer's disease progression via selective enrichment of CD8+ T cells

Cell Rep. 2023 Oct 31;42(10):113313. doi: 10.1016/j.celrep.2023.113313. Epub 2023 Oct 19.

Abstract

This study investigates stress's impact on Alzheimer's disease (AD) using male APP/PS1 transgenic mice. Negative stressors (chronic social defeat, restraint) and positive hedonia (environmental enrichment, EE) were applied. Stress worsens AD pathology, while EE slows progression. Brain RNA sequencing reveals interleukin-6 (IL-6) and IL-10 as key stress-related AD regulators. Flow cytometry shows that the CD8+/CD4+ T cell ratio shifts in response to stress exposure and EE. Stress exposure increases CD8+/CD4+ ratio, opposite to EE. Depletion and enrichment of CD8+ T cells both accelerate AD, indicating immune intervention's negative impact. Stress management and balanced immunity may aid AD therapy, highlighting novel potential treatment.

Keywords: Alzheimer’s disease; CD8(+) T cells; CP: Immunology; CP: Neuroscience; adaptive immunity; enriched environment; immune intervention; innate immunity; mental health; microglia; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Disease Models, Animal
  • Interleukin-6
  • Male
  • Mice
  • Mice, Transgenic

Substances

  • Interleukin-6
  • Amyloid beta-Protein Precursor
  • Amyloid beta-Peptides