Alzheimer's disease genes and proteins associated with resistance and aerobic training: An in silico analysis

Exp Gerontol. 2022 Oct 15:168:111948. doi: 10.1016/j.exger.2022.111948. Epub 2022 Sep 7.


Background: Exercise appears to be a viable intervention for maintaining cognitive function and regaining functional autonomy, and perhaps even contributing to a slower progression of Alzheimer's Disease (AD).

Objective: To explore different neuroplasticity pathways modulated by aerobic and strength training, determine whether signaling pathways overlapped for each specific training method (aerobic and strength training), and evaluate whether there is a functional relationship between APOE and APP gene expression with aerobic training modulated by BDNF; and strength training modulated by IGF-1.

Methods: An in silico analysis was performed to analyze the connection between exercise types and neuroplasticity as a protective factor in AD. The platform provides a protein-protein interaction network translated into known and predicted interactions. A score > 0.70 was determined as high confidence and the network was considered significant when the Protein-Protein Interaction Enrichment was <0.01.

Results: Multiple functional associations considered significant between the analyzed proteins. The results of our gene network model support that exercise, both aerobic and strength, can modulate genes that affect hippocampal neuroplasticity and neurogenesis, which may delay cognitive decline and Alzheimer's related symptoms.

Conclusion: The investigation about the functional association of aerobic training via BDNF in the modulation of APP, APOE, and MAPT genes in the hippocampus seems to be established, while strength training seems to induce the production of IGF-1 and IGF-1R, modulating AKT1.

Keywords: Brain-derived neurotrophic factor; Cognitive aging; Healthy aging; Insulin-like growth factor I; Neurocognitive disorders; Resistance training.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / therapy
  • Apolipoproteins E
  • Brain-Derived Neurotrophic Factor / genetics
  • Cognitive Dysfunction*
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Resistance Training* / methods


  • Apolipoproteins E
  • Brain-Derived Neurotrophic Factor
  • Insulin-Like Growth Factor I