Evidence map›Paper›PMID 42841315›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Genetic evidence supports a cortical neuroprotective role of GLP-1 receptor activation in Alzheimer's disease: A drug-target Mendelian randomization study.

Li Jiang, Xinyuan Chen, Jiangshun Qian, Kaiwen Fang, Chenyuan Dai, Dong Chang, Liang Jin, Wenjin Huang, Yuzheng Wang, Xiaomei Duan and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Li JiangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Xinyuan ChenMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Jiangshun QianMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Kaiwen FangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Chenyuan DaiMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Dong ChangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Liang JinMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Wenjin HuangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Yuzheng WangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Xiaomei DuanMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Juan WanMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Mingqiang LiMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Wendiao ZhangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Jinchen LiBioinformatics Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zijian XiaoMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Heng WuMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Qingtuan MengMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Beisha TangMulti-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.

Funding

China Postdoctoral Science Foundation 2023M741609National Natural Science Foundation of China 82301434
6 · The paper itself

Abstract

introductionWhether glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation lowers Alzheimer's disease (AD) risk via peripheral metabolic improvement or direct neuroprotection remains unclear.

methodsUsing blood and brain-cortex cis-acting expression quantitative trait loci (cis-eQTLs) for GLP-1R as instruments, we performed cis-Mendelian randomization (cis-MR) for AD and seven biomarkers. Mendelian randomization Bayesian model averaging (MR-BMA), cis-multivariable Mendelian randomization (cis-MVMR), and two-step cis-MR assessed 11 metabolic and inflammatory mediators, and tissue-specific cis-MVMR identified the causal tissue.

resultsGLP-1R expression was associated with lower AD risk and cerebrospinal fluid phosphorylated tau (p-tau) levels. The cis-MVMR identified systolic blood pressure as the only independent mediator, whereas GLP-1R retained a direct protective effect on AD. Tissue-specific cis-MVMR attributed the effect predominantly to cortical (posterior inclusion probability [PIP] = 0.998) rather than blood GLP-1R expression (PIP = 0.002).

conclusionGenetic evidence supports GLP-1R as a potential target in AD, with a protective effect not fully explained by peripheral metabolic improvement and possibly involving cortical neuroprotection, supporting further investigation of brain-penetrant agents at preclinical or prodromal stages.

Indexed as

Alzheimer DiseaseCerebral CortexGlucagon-Like Peptide-1 ReceptorBayes TheoremBiomarkersHumansMendelian Randomization AnalysisQuantitative Trait LociBiomarkersGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorAlzheimer's diseasecis‐Mendelian randomizationglucagon‐like peptide‐1 receptor agonists

Identifiers

PMID42841315
PMCPMC13643831

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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.