Evidence map›Paper›PMID 40394225›Full record

ArticleNature aging2025

Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice.

Yun Zhang, Huaqiu Chen, Yijia Feng, Mingjing Liu, Zhi Lu, Bolang Hu, Lifen Chen, Yang Zhang, Jiawen Liu, Fang Cai and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
–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

39 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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.

Yun Zhang *Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. zhangyun_202104@163.com.ORCID http://orcid.org/0009-0004-5878-6939
Huaqiu Chen *National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China.
Yijia Feng *The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China.ORCID http://orcid.org/0000-0002-7668-7350
Mingjing LiuChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Zhi LuDepartment of Nuclear Medicine, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
Bolang HuThe Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China.
Lifen ChenOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Yang ZhangNational Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
Jiawen LiuNational Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China.
Fang CaiOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Yifan ZhaoThe Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China.
Wenhao PanThe Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China.
Xinxin LiaoDepartment of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha, China.
Sipei PanOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Isabel Bestard-LorigadosTownsend Family Laboratories, Department of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
Yili WuThe Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China.
Weihong SongThe Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. weihong@wmu.edu.cn.ORCID http://orcid.org/0000-0001-9928-889X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82201576National Natural Science Foundation of China (National Science Foundation of China) 82230043National Natural Science Foundation of China (National Science Foundation of China) 82293642
6 · The paper itself

Abstract

Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential neuroprotective properties, but their effects on AD and the underlying mechanisms are not well understood. Here we demonstrate that GLP-1RAs can alleviate AD-related phenotypes by activating 5' AMP-activated protein kinase (AMPK) signaling. We found that plasma GLP-1 levels were decreased in AD model mice and negatively correlated with amyloid-beta (Aβ) load in patients with AD. Enhancing GLP-1 signaling through GLP-1RAs increased CaMKK2-AMPK signaling, which subsequently reduced BACE1-mediated cleavage of amyloid precursor protein (APP) and Aβ generation. GLP-1RAs also increased AMPK activity in microglia, inhibiting neuroinflammation and promoting Aβ phagocytosis. Consequently, GLP-1RAs inhibited plaque formation and improved memory deficits in AD model mice. Our findings indicate that AMPK activation mediates the effects of GLP-1RAs on AD, highlighting the therapeutic potential of GLP-1RAs for the treatment of AD.

Indexed as

Alzheimer DiseaseAMP-Activated Protein KinasesGlucagon-Like Peptide-1 Receptor AgonistsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCalcium-Calmodulin-Dependent Protein Kinase KinaseDiabetes Mellitus, Type 2Disease Models, AnimalFemaleGlucagon-Like Peptide 1HumansMaleMiceAMP-Activated Protein KinasesAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBace1 protein, mouseCalcium-Calmodulin-Dependent Protein Kinase KinaseCamkk2 protein, mouseGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor Agonists

Identifiers

PMID40394225

What OpenQuestion holds

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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.