The therapeutic potential of early exercise in Alzheimer's disease: Focus on the brain-spleen axis

IF 15.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2026-01-01 Epub Date: 2025-12-01 DOI:10.1016/j.arr.2025.102980

Tao Wang , Lili Feng , Zhenjun Tian

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引用次数: 0

Abstract

Alzheimer's disease (AD) is the predominant cause of cognitive dysfunction, with global prevalence increasing annually. AD progression is principally driven by the accumulation of amyloid-β (Aβ) and hyperphosphorylated microtubule-associated protein tau (p-Tau), which trigger a subsequent cascade of neuroinflammatory responses within the central nervous system (CNS). This pathological cascade is regulated by reciprocal CNS-peripheral immune crosstalk. The brain-spleen axis has emerged as a critical conduit that orchestrates splenic immune activity and CNS-peripheral immune crosstalk during AD progression. Notably, through the brain-spleen axis, early-life and preclinical exercise may restore splenic vagal-sympathetic homeostasis, re-establish immune equilibrium, and then mitigate neuroinflammation. This review advances a testable hypothesis that early exercise prevents or attenuates AD pathology through the brain-spleen axis, potentially accelerating the development of innovative therapeutic targets such as non-invasive brain stimulation.

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早期运动对阿尔茨海默病的治疗潜力：关注脑脾轴。

阿尔茨海默病（AD）是认知功能障碍的主要原因，全球患病率每年都在增加。AD的进展主要是由淀粉样蛋白-β (a β)和微管相关蛋白tau （p-Tau）的过度磷酸化的积累驱动的，这在中枢神经系统（CNS）内引发随后的级联神经炎症反应。这种病理级联是由中枢神经系统-外周免疫相互串扰调节的。脑-脾轴已成为AD进展过程中协调脾免疫活动和中枢-外周免疫串扰的关键通道。值得注意的是，通过脑-脾轴，早期生活和临床前运动可以恢复脾脏迷走神经-交感神经稳态，重建免疫平衡，从而减轻神经炎症。这篇综述提出了一个可验证的假设，即早期运动通过脑脾轴预防或减轻AD病理，可能加速创新治疗靶点的发展，如非侵入性脑刺激。

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.