ArticleNature genetics2024
Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.
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Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.
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86citing papers in PubMed, 2 pooled it
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Who cites it
86 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.Nature communications · 2026Pooled it
- Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review.Molecular psychiatry · 2025Pooled it
- Single-nucleus atlas of cell-type specific genetic regulation in the human brain.Nature genetics · 2026Article
- Shared genetic architecture of schizophrenia and lupus identifies pleiotropic loci with distinct downstream mechanisms.Human molecular genetics · 2026Article
- A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Genome-wide pQTL mapping in human skin identifies specific genetic regulators and mechanistic links to skin disorders.Nature communications · 2026Article
- Sex-aware causal inference assessment of the immune system in complex neurodegenerative diseases.Brain : a journal of neurology · 2026Article
- Effects of BACE2 polymorphisms on verbal memory in the general population.European archives of psychiatry and clinical neuroscience · 2026Article
- 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
- Longitudinal plasma proteomics separates diagnostic differences from progression-linked changes in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Human IL-34 Deficiency Primes Microglia Toward Alzheimer's Disease-Associated States.medRxiv : the preprint server for health sciences · 2026Article
- Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3.Nature communications · 2026Article
- amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Functionally informed cis and trans proteome-wide association studies prioritize disease-critical genes.Research square · 2026Article
- Proteomic Signatures of ProtectedmedRxiv : the preprint server for health sciences · 2026Article
- Proteomic signatures of the APOE ε4 and APOE ε2 genetic variants and Alzheimer's disease.Nature aging · 2026Article
- Functionally informed cis and trans proteome-wide association studies prioritize disease-critical genes.medRxiv : the preprint server for health sciences · 2026Article
- Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
42 authors.
Daniel WesternDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3725-9553
Jigyasha TimsinaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Lihua WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Ciyang WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5253-0490
Chengran YangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4577-5590
Bridget PhillipsDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-5261-689X
Yueyao WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0003-3288-1180
Menghan LiuDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Muhammad AliDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1399-6631
Aleksandra BericDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9351-585X
Priyanka GorijalaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Pat KohlfeldDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0004-9206-8244
John BuddeDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7778-7276
Allan I LeveyDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-3153-502X
John C MorrisDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Richard J PerrinDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-3443-7716
Agustin RuizACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2633-2495
Marta MarquiéACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Mercè BoadaACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Itziar de RojasACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Jarod RutledgeWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7790-2801
Hamilton OhWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8192-7593
Edward N WilsonWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0640-5247
Yann Le GuenDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6649-8364
Lianne M ReusAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-6936-242X
Betty TijmsAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-2612-1797
Pieter Jelle VisserAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Sven J van der LeeAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-1606-8643
Yolande A L PijnenburgAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Charlotte E TeunissenNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Location VUmc, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-4061-0837
Marta Del Campo MilanDepartamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo CEU, CEU Universities, Madrid, Spain.ORCID http://orcid.org/0000-0003-2808-3699
Ignacio AlvarezMemory Disorders Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Spain.ORCID http://orcid.org/0000-0002-8537-3935
Miquel AguilarMemory Disorders Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Spain.
Dominantly Inherited Alzheimer Network (DIAN)
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Michael D GreiciusWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Pau PastorMemory Disorders Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Spain.ORCID http://orcid.org/0000-0002-7493-8777
David J PulfordMedicines R&D, GlaxoSmithKline, Stevenage, UK.ORCID http://orcid.org/0000-0002-6998-4883
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Tony Wyss-CorayWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5893-0831
Yun Ju SungDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8021-4070
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. cruchagac@wustl.edu.ORCID http://orcid.org/0000-0002-0276-2899
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MStanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0MResearch Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI Susan Lynn Stark · 2020 to 2026
$28.7MDissecting the Genomic Etiology of non-Mendelian Early-Onset Alzheimer Disease and Related PhenotypesR01AG064614 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BEECHAM, GARY WAYNE, CRUCHAGA, CARLOS · 2019 to 2023
$11.5MIdentification and Characterization of Cell-Specific Transposable Elements Implicated on Alzheimer Disease and Healthy AgingR01AG078964 · NIA · WASHINGTON UNIVERSITY · PI Carlos Cruchaga, Bess Frost · 2022 to 2026
$9.0MUSING 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
$2.7MAlzheimer's Association ZEN-22-848604NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066515NIA NIH HHS R00 AG062723NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG064614NIA NIH HHS R01 AG074007NIA NIH HHS R01 AG078964NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG071706NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG058922NIA NIH HHS U19 AG032438U.S. Department of Health & Human Services | National Institutes of Health (NIH) P01AG003991U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG044546U.S. Department of Health & Human Services | National Institutes of Health (NIH) RF1AG053303U.S. Department of Health & Human Services | National Institutes of Health (NIH) RF1AG058501U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01AG058922
Abstract
The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples. We identified 3,885 associations for 1,883 proteins, including 2,885 new pQTLs, demonstrating unique genetic regulation in CSF. We identified CSF-enriched pleiotropic regions on chromosome (chr)3q28 near OSTN and chr19q13.32 near APOE that were enriched for neuron specificity and neurological development. We integrated our associations with Alzheimer's disease (AD) through proteome-wide association study (PWAS), colocalization and Mendelian randomization and identified 38 putative causal proteins, 15 of which have drugs available. Finally, we developed a proteomics-based AD prediction model that outperforms genetics-based models. These findings will be instrumental to further understand the biology and identify causal and druggable proteins for brain and neurological traits.
Indexed as
Alzheimer DiseaseGenome-Wide Association StudyProteogenomicsQuantitative Trait LociAgedApolipoproteins EFemaleGenetic Predisposition to DiseaseHumansMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideProteomeApolipoproteins EProteome
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