Effects of Exercise Training on Immune-Related Genes and Pathways in the Cortex of Animal Models of Alzheimer's Disease: A Systematic Review

J Alzheimers Dis. 2024;98(4):1219-1234. doi: 10.3233/JAD-230803.


Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that affects the immune system due to the accumulation of amyloid-β (Aβ) and tau associated molecular pathology and other pathogenic processes. To address AD pathogenesis, various approaches had been conducted from drug development to lifestyle modification to reduce the prevalence of AD. Exercise is considered a prominent lifestyle modification to combat AD.

Objective: This observation prompted us to review the literature on exercise related to immune genes in the cortex of animal models of AD. We focused on animal model studies due to their prevalence in this domain.

Methods: The systematic review was conducted according to PRISMA standards using Web of Science (WoS) and PubMed databases. Any kind of genes, proteins, and molecular molecules were included in this systematic review. The list of these immune-related molecules was analyzed in the STRING database for functional enrichment analysis.

Results: We found that 17 research studies discussed immune-related molecules and 30 immune proteins. These studies showed that exercise had the ability to ameliorate dysfunction in AD-related pathways, which led to decreasing the expression of microglia-related pathways and Th17-related immune pathways. As a result of decreasing the expression of immune-related pathways, the expression of apoptosis-related pathways was also decreasing, and neuronal survival was increased by exercise activity.

Conclusions: Based on functional enrichment analysis, exercise not only could reduce apoptotic factors and immune components but also could increase cell survival and Aβ clearance in cortex samples. PROSPERO ID: CRD42022326093.

Keywords: Alzheimer’s disease; Th17-related pathway; apoptosis-related pathway; brain; microglia-related pathway; physical activity.

Publication types

  • Systematic Review

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Disease Models, Animal
  • Exercise
  • Neurodegenerative Diseases*


  • Amyloid beta-Peptides