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Treadmill exercise rescues cognitive deficits in Alzheimer's mice by repairing axonal mitochondrial transport and synaptic function.

Created on 03 Sep 2026

Authors

Baixia Li, Zhiling Zhang, Hegui Bao, Yiran Wang, Xinming Ye, Haixia Tu, Wen Fang

Published in

Neuroreport. Sep 01, 2026. Epub Sep 01, 2026.

Abstract

Alzheimer's disease is a progressive neurological disorder characterized by synaptic injury and loss in its early stage. This study aimed to investigate the effects of treadmill exercise on Alzheimer's disease mice, focusing on the related molecular mechanism of axonal transport.
In this study, 3-month-old male APP/PS1 mice and C57BL/6J mice were used and divided into four groups (n = 9). Behavioral performance was evaluated using the Morris water maze, open field test, and tail suspension test. Transmission electron microscopy and ELISA were used to assess the morphology and function of mitochondria and synapses, individually. The colocalization of mitochondria and synapses was analyzed by double-labeling immunofluorescence. Finally, the underlying mechanism of treadmill exercise on Alzheimer's disease mice was evaluated by Western blotting.
APP/PS1 mice exhibited significant deficits in spatial learning and memory, accompanied by abnormal ultrastructure and dysfunction in hippocampal mitochondria and synapses. Treadmill exercise could ameliorate cognitive impairments and affective disorders in Alzheimer's disease mice, reduce amyloid-beta levels, improve the morphology and function of mitochondria and synapses, and enhance mitochondrial axonal transport, which might be regulated by the related proteins of kinesins, syntabulin, and dyneins.
These results suggest that exercise-induced modulation of mitochondrial dynamics can provide neuroprotection and support the development of novel therapeutic strategies for Alzheimer's disease (Video Abstract, SDC 1).

PMID:
42689376
Bibliographic data and abstract were imported from PubMed on 03 Sep 2026.

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