ArticleMolecular neurodegeneration2024
Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.
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Article in Molecular neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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37citing papers in PubMed, 2 pooled it
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.Nature communications · 2026Pooled it
- Association of soluble TREM2 with Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Genetic Prioritization of Plasma Proteins Across Dementia Subtypes: A Proteome-Wide Mendelian Randomization and Bayesian Colocalization Analysis.Cellular and molecular neurobiology · 2026Article
- Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.Nature genetics · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Proteomic signatures of protected APOE ε4 carriers reveal causal pathways associated with delayed Alzheimer's disease onset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Microglial sTREM2 limits dyskinesia and acts on TrkB to support circuit plasticity.bioRxiv : the preprint server for biology · 2026Article
- Proteomic Signatures of ProtectedmedRxiv : the preprint server for health sciences · 2026Article
- Low overlap of plasma and CSF protein quantitative trait loci affects protein discovery for neurological disease.Science translational medicine · 2026Article
- APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Analyses of plasma multi-omic data across ancestries identify novel pathways implicated in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Targeting microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and therapeutic approaches.Frontiers in immunology · 2026Review
- Revisiting TREM2: from multi-omics signaling networks to clinical translation.Frontiers in immunology · 2026Review
- Alterations in the brain lipidome of Alzheimer's disease donors with rareBrain communications · 2026Article
- Molecular mechanism of Alzheimer's disease using integrated multi-omics.Frontiers in aging neuroscience · 2026Review
- Integrative Genetic, Proteogenomic, and Multi-omics Analyses Reveal Sex-Biased Causal Genes and Drug Targets in Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2025Article
- Integrating Genomic, eQTL, and Mendelian Randomization Analyses to Identify Microglial Drug Targets in Multiple Sclerosis.Journal of cellular and molecular medicine · 2025Article
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
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Authors and funding
33 authors at 9 institutions in 3 countries.
Lihua Wang *Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Niko-Petteri Nykänen *Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Daniel WesternDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Priyanka GorijalaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Jigyasha TimsinaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Fuhai LiDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Zhaohua WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Muhammad AliDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Chengran YangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Menghan LiuDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
William BrockDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Marta MarquiéNetworking Research Center on Neurodegenerative Disease (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Mercè BoadaNetworking Research Center on Neurodegenerative Disease (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Ignacio AlvarezMemory Disorders Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Spain.
Miquel AguilarMemory Disorders Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Spain.
Pau PastorUnit of Neurodegenerative diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain.
Agustín RuizNetworking Research Center on Neurodegenerative Disease (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Raquel PuertaNetworking Research Center on Neurodegenerative Disease (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Adelina OrellanaNetworking Research Center on Neurodegenerative Disease (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Jarod RutledgeWu-Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Hamilton OhWu-Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Michael D GreiciusWu-Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Yann Le GuenWu-Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Richard J PerrinDepartment of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Tony Wyss-CorayWu-Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Angela JeffersonVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Timothy J HohmanVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Neill Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Hiroshi MoriNagaoka Sutoku University, Osaka, Japan.
Alison GoateDepartment of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Johannes LevinDepartment of Neurology, University Hospital of Munich, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany.
Yun Ju SungDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. cruchagac@wustl.edu.ORCID 0000-0002-0276-2899
Washington University in St. Louis · USInstituto de Salud Carlos III · ESNeurosciences Institute · USUniversity Hospital Mútua de Terrassa · ESVanderbilt University Medical Center · USIcahn School of Medicine at Mount Sinai · USInstitut d'Investigació en Ciències de la Salut Germans Trias i Pujol · ESLudwig-Maximilians-Universität München · DEWinnMed · US
Funding
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5MGenetic Architecture of Alzheimer’s disease ProteinopathiesR01AG064877 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CRUCHAGA, CARLOS, KAMBOH, M. ILYAS · 2021 to 2024
$8.4MIdentification and characterization of AD risk networks using multi-dimensional "omics" dataU01AG052411 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2016 to 2020
$4.5MUSING QUANTITATIVE TRAITS TO IDENTIFY NOVEL GENES FOR ALZHEIMERS DISEASE AND OTHER COMPLEX TRAITSRF1AG053303 · NIA · WASHINGTON UNIVERSITY · PI CLIMER, SHARLEE, CRUCHAGA, CARLOS · 2016 to 2020
$4.0MGENETIC MODIFIERS OF CEREBROSPINAL FLUID TREM2 IN ALZHEIMER'S DISEASERF1AG058501 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, PICCIO, LAURA · 2018 to 2018
$3.5MThe Familial Alzheimer Sequencing (FASe) ProjectU01AG058922 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2018 to 2022
$3.5MSex-specific Molecular Profiling to Understand Pathology and Identify Causal Genes and Drug Targets for Alzheimer's DiseaseRF1AG074007 · NIA · WASHINGTON UNIVERSITY · PI SUNG, YUNJU · 2021 to 2021
$2.7MIDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7MDepartment of Defense LI‑ W81XWH2010849NIA NIH HHS P01 AG003991NIA NIH HHS R01 AG044546NIA NIH HHS R01AG044546NIA NIH HHS R01 AG064877NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A) that drive the association in MS4A locus and showed an epistatic effect for sTREM2 levels and AD risk. The novel TREM2 locus on chr 6 contains two rare missense variants (rs75932628 p.R47H, P=7.16×10
Indexed as
Alzheimer DiseaseApolipoproteins EBiomarkersGenome-Wide Association StudyHumansMembrane GlycoproteinsMicrogliaReceptors, ImmunologicReceptor, Transforming Growth Factor-beta Type IIApolipoproteins EBiomarkersMembrane GlycoproteinsReceptors, ImmunologicReceptor, Transforming Growth Factor-beta Type IITREM2 protein, human
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