Abstract
Background Type 2 diabetes is associated with increased Alzheimer’s disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer’s disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer’s disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective of this review was to identify what evidence exists that examines the association between insulin, physical activity, Aβ and tau in research conducted on animal models and in human cohorts. We specifically aimed to identify whether insulin resistance has a mediating role in the relationship between physical activity and Aβ and tau. Methods A systematic search was performed in Cochrane library, PsycINFO, PubMed and World of Science to identify publications. The search identified 343 articles with 20 articles meeting the full inclusion criteria. Results Most animal studies showed that exercise could simultaneously reduce insulin resistance and Alzheimer’s disease pathology and/or biomarkers. We found limited evidence from human research that physical activity was associated with both reduced insulin resistance and Aβ or tau levels. We did not find any evidence that insulin resistance mediates the physical activity – Aβ or tau relationship. Conclusion Exercise can simultaneously impact insulin resistance and Alzheimer’s disease pathology in animal models. Results from human research are limited, and no robust evaluation of the potential mediating role of insulin resistance in the physical activity – Aβ or tau relationship exists. Future research should focus on identifying the mediating pathways that may link physical activity to biomarkers of Alzheimer’s disease.
Document Type
Journal Article
Date of Publication
1-1-2026
Volume
114
PubMed ID
41297615
Publication Title
Ageing Research Reviews
Publisher
Elsevier
School
School of Medical and Health Sciences
Funders
Research Training Program / National Health and Medical Research Council
Grant Number
NHMRC Number : GNT1197315
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Comments
Slee, M. G., Scotney, J., Rainey-Smith, S. R., Erickson, K. I., Sohrabi, H. R., Verdile, G., & Brown, B. M. (2025). Insulin resistance as a mediator of physical activity’s effects on beta-amyloid accumulation and tau phosphorylation: A scoping review. Ageing Research Reviews, 114, 102956. https://doi.org/10.1016/j.arr.2025.102956