Insulin resistance as a mediator of physical activity's effects on beta-amyloid accumulation and tau phosphorylation: A scoping review

IF 15.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI:10.1016/j.arr.2025.102956

Michael G. Slee , Joanne Scotney , Stephanie R. Rainey-Smith , Kirk I. Erickson , Hamid R. Sohrabi , Giuseppe Verdile , Belinda M. Brown

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引用次数: 0

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.

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胰岛素抵抗作为身体活动对β -淀粉样蛋白积累和tau蛋白磷酸化影响的中介：范围综述

背景2型糖尿病与阿尔茨海默病风险增加和脑β淀粉样蛋白（Aβ）负担相关，提示阿尔茨海默病和2型糖尿病之间存在潜在的机制关系。动物研究表明，运动可以降低大脑中Aβ和tau蛋白的水平，而人类研究在一定程度上是有限的，一些研究已经报告了体育活动与较低的大脑Aβ和tau蛋白水平有关。锻炼与降低胰岛素抵抗有很好的联系；因此，由于体育活动可以影响胰岛素抵抗和阿尔茨海默病病理和/或生物标志物，因此有理由假设可能存在中介关系。本综述的目的是确定在动物模型和人类队列研究中存在哪些证据可以检验胰岛素、身体活动、Aβ和tau之间的关联。我们特别旨在确定胰岛素抵抗是否在身体活动与a β和tau之间的关系中起中介作用。方法系统检索Cochrane library、PsycINFO、PubMed、World of Science等文献。检索发现343篇文章，其中20篇符合全部纳入标准。结果大多数动物研究表明，运动可以同时降低胰岛素抵抗和阿尔茨海默病的病理和/或生物标志物。我们从人类研究中发现有限的证据表明，体育活动与降低胰岛素抵抗和Aβ或tau水平有关。我们没有发现任何证据表明胰岛素抵抗介导身体活动- Aβ或tau的关系。结论运动可同时影响动物模型的胰岛素抵抗和阿尔茨海默病病理。人类研究的结果有限，并且没有关于胰岛素抵抗在身体活动- Aβ或tau关系中的潜在中介作用的可靠评估。未来的研究应侧重于确定可能将体育活动与阿尔茨海默病的生物标志物联系起来的中介途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.