Evidence map›Paper›PMID 42764449›Full record

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

Genetic evidence suggests a protective role of immunoglobulin M in Alzheimer's disease.

Shihui Peng, Guillaume Butler-Laporte, Sterling C Johnson, Corinne D Engelman, Tianyuan Lu

Abstract read
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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.

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0citing papers in PubMed
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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

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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

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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

5 authors.

Shihui PengDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Guillaume Butler-LaporteDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
Sterling C JohnsonDivision of Geriatrics and Gerontology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Corinne D EngelmanDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Tianyuan LuDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID https://orcid.org/0000-0002-5664-5698

Funding

Statistical Data Enclave CoreP30AG017266 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Michal Engelman · 1999 to 2026
$17.0M
Scientific and Technical CoreP2CHD047873 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI Katherine J. Curtis · 2014 to 2026
$5.1M
Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's DiseaseRF1AG054047 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ENGELMAN, CORINNE D. · 2022 to 2025
$3.8M
Advancing statistical genetics tools for reliable drug target discovery and treatment optimizationR35GM162188 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Tianyuan Lu · 2026 to 2026
$414k
NIA NIH HHS P30 AG017266NIA NIH HHS RF1 AG054047NICHD NIH HHS P2C HD047873NIGMS NIH HHS R35 GM162188NIH HHS R35GM162188NIH HHS RF1AG054047of the National Institutes of Healththe Center for Demography and Ecology P2CHD047873the Center for Demography of Health and Aging P30AG017266Wellcome Trust
6 · The paper itself

Abstract

introductionImmune dysfunction has been implicated in Alzheimer's disease (AD), but the roles of specific immunoglobulin classes remain unclear.

methodsWe integrated human genetics and plasma biomarker analyses to evaluate immunoglobulin G (IgG), IgA, and IgM in relation to AD. Two-sample Mendelian randomization analyses were conducted with multiple sensitivity analyses. Polygenic risk scores for immunoglobulin classes were developed in the All of Us Research Program and tested in the UK Biobank for associations with AD and dementia, and in two Wisconsin-based cohorts for associations with plasma amyloid beta (Aβ)42/40, phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).

resultsHigher genetically proxied IgM was consistently associated with lower AD risk, higher Aβ42/40, and lower p-tau217, but not with NfL or GFAP. No consistent associations were observed for IgG or IgA. DISCUSSION: IgM-related humoral immunity may play a protective role in AD and warrants exploration for early intervention and prevention.

Indexed as

Alzheimer DiseaseImmunoglobulin MAgedAmyloid beta-PeptidesBiomarkersFemaleGenetic Risk ScoreGlial Fibrillary Acidic ProteinHumansImmunoglobulin GMaleMendelian Randomization AnalysisNeurofilament ProteinsPeptide Fragmentstau ProteinsAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinImmunoglobulin GImmunoglobulin Mneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer's diseaseamyloid betaimmunoglobulin MMendelian randomizationplasma biomarkerspolygenic risk scoretau

Identifiers

PMID42764449
PMCPMC13590935

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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.