Evidence map›Paper›PMID 40713754›Full record

ArticleTranslational neurodegeneration2025

Long-term exercise enhances meningeal lymphatic vessel plasticity and drainage in a mouse model of Alzheimer's disease.

Yan Chen, Jiachen Cai, Yuzhu She, Xiaoxin He, Hu Feng, Xuewei Li, Yiran Wei, Yi Fan, Wen-E Zhao, Mengmei Yin and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

9 citing papers in PubMed.

  1. Review
  2. [Research progress on vascular endothelial growth factor C in meningeal lymphatic vessel-mediated clearance of amyloid β-protein].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026
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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

17 authors.

Yan ChenJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Jiachen CaiJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Yuzhu SheJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Xiaoxin HeJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Hu FengJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Xuewei LiInstitute of Brain Science and Brain-Inspired Research, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.
Yiran WeiInstitute of Brain Science and Brain-Inspired Research, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.
Yi FanDepartment of Neurology, Brain Institute, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.
Wen-E ZhaoDepartment of Analytical and Testing Center, Nanjing Medical University, Nanjing, 211166, China.
Mengmei YinJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Linjuan YuanJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Yuxi JinJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Fengfei DingDepartment of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Chengyu ShengJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Junying GaoJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China. gaojunying@njmu.edu.cn.
Qian LiJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China. liqian2019@njmu.edu.cn.
Ming XiaoJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China. mingx@njmu.edu.cn.ORCID http://orcid.org/0000-0001-5528-9102

Funding

National Natural Science Foundation of China 81871117National Natural Science Foundation of China 82071199National Natural Science Foundation of China 82204365National Natural Science Foundation of China 82471608Natural Science Foundation of Jiangsu Province BK20230057Natural Science Research of Jiangsu Higher Education Institutions of China 23KJB310009Postdoctoral Innovation Project of Shandong Province SDBX2023056Shandong Provincial Postdoctoral Science Foundation SDCX-ZG-202400044
6 · The paper itself

Abstract

backgroundMeningeal lymphatic drainage is crucial for the clearance of amyloid β (Aβ), supporting the maintenance of brain homeostasis. This makes it a promising therapeutic target for Alzheimer's disease (AD). Long-term exercise can reduce the risk of AD; however, the underlying mechanism is not fully understood. In this study, we investigated whether exercise alleviates AD-related pathological changes by improving meningeal lymphatic drainage and its potential mechanisms.

methodsThe morphological and functional features of meningeal lymphatic vessels, as well as Aβ and reactive gliosis in the brain, were compared between 6.5-month-old 5 × FAD mice with or without 1 month of treadmill exercise. RNA sequencing, protein interactions analysis, gene knockdown mediated by adeno-associated virus, and lymphatic endothelial cell culture were conducted to investigate the mechanism underlying exercise-induced meningeal lymphatic vessel plasticity in 5 × FAD mice.

resultsThe structural integrity of meningeal lymphatic vessels was compromised in 5 × FAD mice, compared with the wild-type mice. Treadmill exercise increased the diameter and the drainage capacity of the meningeal lymphatic vessels, reduced Aβ deposition, reactive gliosis and astrocyte senescence in the hippocampus and frontal cortex, and improved cognitive function of 5 × FAD mice. Mechanistically, thrombospondin-1 (TSP-1) exacerbated the inhibitory effect of Aβ on lymphatic vessel formation and plasticity through interactions with CD36 and CD47, respectively. Exercise decreased the expression of TSP-1 in reactive astrocytes of AD mice by downregulating eleven-nineteen lysine-rich leukemia-associated factor 2 (EAF2), a protein that facilitates the transcription of the TSP-1-encoding gene Thbs-1 by binding p53. Ultimately, we found that hippocampal astrocyte-specific knockdown of Thbs-1 or Eaf2 enhanced meningeal lymphatic drainage and alleviated AD-like pathology in the hippocampus of 5 × FAD mice.

conclusionsLong-term exercise protects against AD by enhancing the plasticity and drainage of meningeal lymphatic vessels through downregulation of the EAF2-p53-TSP-1 pathway associated with reactive astrocytes.

Indexed as

Alzheimer DiseaseLymphatic VesselsMeningesPhysical Conditioning, AnimalAmyloid beta-PeptidesAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, TransgenicAmyloid beta-PeptidesAlzheimer's diseaseEAF2-p53-TSP-1LymphangiogenesisMeningeal lymphaticsTreadmill exercise

Identifiers

PMID40713754
PMCPMC12291319

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.