Evidence map›Paper›PMID 40556345›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Voluntary wheel running exercise improves sleep disorder, circadian rhythm disturbance, and neuropathology in an animal model of Alzheimer's disease.

Yiying Hu, Long Niu, Yixin Chen, Huijia Yang, Xinhui Qiu, Fei Jiang, Cong Liu, Huaibin Cai, Weidong Le

Abstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  6. Timing the decline: Cellular circadian rhythms and Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yiying HuKey Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Long NiuKey Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Yixin ChenKey Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Huijia YangKey Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Xinhui QiuKey Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Fei JiangDalian Seventh People's Hospital, Dalian, China.
Cong LiuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Huaibin CaiTransgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Weidong LeCenter for Clinical and Translational Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China.

Funding

Fundamental Research Funds for Central Universities of the Central South University YDZX20213100001002life and health guidance program of Dalian city 2024ZDJH01PT066National Natural Science Foundation of China 32220103006National Natural Science Foundation of China 82271524the intramural research program of National Institute on Aging, NIH AG000540the intramural research program of National Institute on Aging, NIH HC
6 · The paper itself

Abstract

introductionThe sleep-wake cycle and circadian rhythm disturbances are common in Alzheimer's disease (AD). However, it is not known if exercise has any benefit for the sleep disorders in AD.

methodsWe conducted a 2-month voluntary wheel running (VWR) exercise (Ex) in an animal model of AD (APP

resultsAfter VWR exercise in the AD mice, the rapid eye movement sleep was increased by 89%. The levels of circadian clock genes were significantly changed (brain and muscle arnt-like protein 1 [BMAL1] and retinoic acid receptor-related orphan receptorsα [RORα] reduced by 45.7% and 36.4%, reverse erythroblastosis virusα (REV-ERBα) increased by 119%) in the SCN by immunofluorescence staining, with the mRNA levels were markedly altered (Bmal1 and Rorα decreased by 57% and 68%, Rev-erbα elevated by 79%) in the hypothalamus at Zeitgeber Time 1; phospho-tau 231 (p-tau231) was reduced by 35%, whereas vesicular GABA transporter (VGAT) was elevated by 38.7% in the SCN. In addition, ionized calcium binding adapter molecude 1 (Iba1), glial fibrillary acidic protein (GFAP), amyloid β (Aβ), and p-tau231 were significantly reduced in the hippocampus and cortex. DISCUSSION: Our results demonstrate that VWR exercise improves sleep disorders, cognitive deficits, and neuropathology in AD mice. HIGHLIGHTS: Voluntary wheel running (VWR) exercise improves the behavioral circadian rhythm disorder and sleep structure disturbance in Alzheimer's disease (AD) mice. After VWR exercise, there is a significant change in the expression levels of circadian clock genes, and a remarkable reduction of tau phosphorylation and axonal damage in the γ-aminobutyric acid (GABA)ergic neurons in the suprachiasmatic nucleus (SCN). The levels of beta-site amyloid precurson protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β) are reduced in the hypothalamus after VWR exercise in AD mice. Furthermore, VWR exercise attenuates cognitive deficits, neuroinflammation, amyloid beta (Aβ), and phospho-tau protein accumulation in the hippocampus and cortex.

Indexed as

Alzheimer DiseaseBrainChronobiology DisordersPhysical Conditioning, AnimalSleep Wake DisordersAnimalsCircadian RhythmDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, TransgenicSuprachiasmatic NucleusAlzheimer's diseasecircadian rhythmsleep–wake cyclesuprachiasmatic nucleusvoluntary wheel running exercise

Identifiers

PMID40556345
PMCPMC12187974

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.