Evidence mapPaperPMID 41965693Full record

ArticleJournal of translational medicine2026

Targeting the astrocyte-microglia EFEMP1-GALNT10 axis: a spatially programmable therapeutic strategy for hippocampal vulnerability in Alzheimer's disease.

Junting Liu, Jing Liu, Yujian Fan, Congcong Liu, Jingrong Cao, Haixia Ma, Yuli Hou, Shuo Gao, Peichang Wang

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Article in Journal of translational medicine, 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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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Junting LiuDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Jing LiuDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Yujian FanDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Congcong LiuDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Jingrong CaoDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Haixia MaDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Yuli HouDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Shuo GaoDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Peichang WangDepartment of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China. pcw1905@126.com.ORCID http://orcid.org/0000-0002-7970-9797

Funding

Natural Science Foundation of Beijing Municipality L246009The State Key Program of the National Natural Science Foundation of China grants 82030064
6 · The paper itself

Abstract

backgroundThe hippocampus is selectively vulnerable to Alzheimer’s disease (AD), but the spatially resolved, cell-type-specific drivers of this susceptibility remain unknown, hindering the development of targeted therapies.

methodsWe employed an integrated causal-spatial approach, combining single-nucleus RNA sequencing (snRNA-seq) from 53 post-mortem AD brains, multi-omics triangulation (Mendelian randomization and Bayesian colocalization), and cross-species spatial mapping in human cohorts and 5xFAD mice to identify drivers of hippocampal vulnerability.

resultsWe identified a novel astrocyte-microglia co-pathology axis centered on EFEMP1 and GALNT10. Causal inference prioritized this axis, supported by an EFEMP1 plasma protein quantitative trait locus (pQTL) with an exceptional effect size (OR = 7.96) and dual epigenetic-transcriptional regulation of microglial GALNT10. The axis demonstrated hippocampus-specific co-expression in humans (R = 0.81, p < 0.001), pathological amplification in 5xFAD mice (tM1 = 0.77 ± 0.04 vs. WT 0.69 ± 0.04, p < 0.001), and focal enrichment near Aβ plaques (EFEMP1: r = -0.79; GALNT10: r = -0.67, p < 0.001). Mechanistically, it forms a core interactome with EGFR and TIMP3, coupling extracellular matrix (ECM) dysregulation with neuroinflammation.

conclusionsOur study defines the EFEMP1-GALNT10 axis as a spatially coordinated driver of hippocampal vulnerability in AD. The integrated causal-spatial pipeline provides a generalizable framework for translating genetic associations into spatially resolved therapeutic targets.

Indexed as

Alzheimer DiseaseAstrocytesExtracellular Matrix ProteinsHippocampusMicrogliaN-AcetylgalactosaminyltransferasesAnimalsHumansMiceMice, TransgenicQuantitative Trait LociEFEMP1 protein, humanExtracellular Matrix ProteinsN-AcetylgalactosaminyltransferasesAlzheimer’s diseaseAstrocyte-microglia crosstalkCausal inferenceEFEMP1-GALNT10 axisHippocampal vulnerabilityMulti-omics integrationSingle-cell genomics

Identifiers

PMID41965693
PMCPMC13214142

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.