Evidence map›Paper›PMID 42361163›Full record

ArticleScience advances2026

Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.

Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu and 42 more

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In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

52 authors.

Cassandra O BlewLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0009-0008-9840-5298
Michael R DugganLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-1029-4423
Dimitrios TsitsipatisLaboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0009-0002-6399-034X
Gabriela T GomezDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1761-0070
Zulema Rodriguez-HernandezInstitute of Epidemiology and Prevention, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.ORCID 0000-0003-0720-384X
Luke C PillingDepartment of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.ORCID 0000-0002-3332-8454
Jingsha ChenDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Eva JacobsenIcelandic Heart Association, Kopavogur, Iceland.ORCID 0009-0003-6533-2444
Heather E DarkLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0001-7194-3637
Yifei LuDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Shannon M DrouinLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Cassandra M JoynesLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Minhao YaoCentre for Quantitative Medicine, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
Murat BilgelLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0001-5042-7422
Abhay MoghekarDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-9464-1551
Qu TianTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0003-2706-1439
Julián CandiaTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0001-5793-8989
Mary KailehLaboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Aditi GuptaLaboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0009-0008-6875-8981
Krystyna Mazan-MamczarzLaboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0009-0005-1545-0500
Myriam GorospeLaboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0001-5439-3434
Alexey LyashkovTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Yevgeniya LukyanenkoTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Mika KivimakiBrain Sciences, University College London, London, England, UK.ORCID 0000-0002-4699-5627
Philipp FrankBrain Sciences, University College London, London, England, UK.ORCID 0000-0001-8824-8673
Lori L JenningsNovartis, Cambridge, MA, USA.ORCID 0000-0001-5130-8417
Valborg GudmundsdottirIcelandic Heart Association, Kopavogur, Iceland.ORCID 0000-0002-7459-1603
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland.ORCID 0000-0001-5696-0084
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.ORCID 0000-0002-3238-7612
Naoto KanekoNEC Solution Innovators Limited, Koto-ku, Tokyo, Japan.ORCID 0009-0005-3194-4156
Shintaro KatoNEC Solution Innovators Limited, Koto-ku, Tokyo, Japan.ORCID 0000-0001-6240-1326
Makio FuruichiNEC Solution Innovators Limited, Koto-ku, Tokyo, Japan.
Masaki ShibayamaNEC Solution Innovators Limited, Koto-ku, Tokyo, Japan.
Masahisa KatsunoDepartment of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.ORCID 0000-0001-9453-9311
Keita HiragaDepartment of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.ORCID 0000-0002-0134-2956
Yukiko NishitaDepartment of Epidemiology of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.ORCID 0000-0002-2551-9605
Rei OtsukaDepartment of Epidemiology of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
James R PikeOptimal Aging Institute, New York University Grossman School of Medicine, New York, NY, USA.ORCID 0000-0002-6858-620X
Mary R RooneyDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0002-5607-4848
Pascal SchlosserInstitute of Epidemiology and Prevention, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-8460-0462
Yuhan CuiArtificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0017-0056
Guray ErusArtificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-6633-4861
Christos DavatzikosArtificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-1025-8561
Rebecca F GottesmanStroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.ORCID 0000-0002-9504-1256
Iwao WagaNEC Solution Innovators Limited, Koto-ku, Tokyo, Japan.
Priya PaltaDepartment of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0009-0006-7153-5100
Christie BallantyneSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-6432-1730
Michael GriswoldDepartment of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.ORCID 0000-0001-8106-5516
Zhonghua LiuDepartment of Biostatistics, Columbia University, New York, NY, USA.ORCID 0000-0003-3048-9823
Luigi FerrucciTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-6273-1613
Allison B HermanLaboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Keenan A WalkerLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-5989-9853

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
Improving diabetes prediction using clinical factors, proteomic biomarkers, and polygenic risk scoresK01DK141963 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Mary R Rooney · 2025 to 2026
$313k
NIA NIH HHS P30 AG066507NIDDK NIH HHS K01 DK141963
6 · The paper itself

Abstract

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. Exposure of cultured myeloid cells to recombinant GDF15 altered biological pathways that we subsequently demonstrated are predictive of dementia risk, including interferon/antiviral responses. These findings support circulating GDF15's role as an early biomarker-particularly for vascular dementia and neuroinflammation-and identify the mechanisms by which it may drive dementia risk.

Indexed as

DementiaGrowth Differentiation Factor 15NeuroimmunomodulationSignal TransductionAlzheimer DiseaseBiomarkersFemaleHumansMaleMendelian Randomization AnalysisRisk FactorsBiomarkersGDF15 protein, humanGrowth Differentiation Factor 15

Identifiers

PMID42361163
PMCPMC13308606

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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.