ArticleNeuron2025
Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum.
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Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51citing papers in PubMed
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Who cites it
51 citing papers in PubMed.
- MIND diet-related plasma proteins are associated with Alzheimer's disease risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Plasma proteomic profiles of Alzheimer's disease and neurodegeneration in African cohorts.Nature communications · 2026Article
- Blood-based proteomic signature of amyloidosis: identification of novel regulators of amyloid load.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Polyol pathway dysregulation in CSF links glucose metabolism to tau pathology independently of amyloid and genetic predisposition.medRxiv : the preprint server for health sciences · 2026Article
- A diagnostic plasma omics-biomarker for Alzheimer's disease informed by microglial single-cell transcriptomics: A pilot study.bioRxiv : the preprint server for biology · 2026Article
- GPND-AI NULISA: A 15-Protein AI classifier for diagnosis and co-pathology profiling across neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026Article
- Reproducibility-driven discovery and systematic benchmarking reveal a robust cerebrospinal fluid proteomic signature in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Red Macroalgae as Sources of Antioxidant and Multifunctional Ingredients for Functional Foods: A Biorefinery Approach.Marine drugs · 2026Article
- Clinical impact of the Alzheimer's Disease Neuroimaging Initiative: A review of studies using ADNI data (2023 to June 2025).Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CSF microtubule-associated protein 1 light chain 3A and 3B levels are associated with tau pathology and Alzheimer's disease risk through amyloid deposition and microglial signaling.Journal of neuroinflammation · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- Article
- Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.medRxiv : the preprint server for health sciences · 2026Article
- Brain capillary endothelial-like cells show altered barrier functionality and reduced transport of amyloid β in late-onset Alzheimer disease.Fluids and barriers of the CNS · 2026Article
- The Impact of Structural Variation on Alzheimer's Disease in the Alzheimer's Disease Sequencing Project.Research square · 2026Article
Corrections and comments
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Authors and funding
34 authors.
Muhammad AliDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Jigyasha TimsinaDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Daniel WesternDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Menghan LiuDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Aleksandra BericDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
John BuddeDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Anh DoDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Gyujin HeoDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Lihua WangDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Jen GentschDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Suzanne E SchindlerDepartment of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
John C MorrisDepartment of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
David M HoltzmanDepartment of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Agustin RuizACE Alzheimer Center Barcelona, Barcelona, Spain.
Ignacio AlvarezFundació Docència i Recerca Mútua de Terrassa, Terrassa, Barcelona, Spain.
Miquel AguilarFundació Docència i Recerca Mútua de Terrassa, Terrassa, Barcelona, Spain.
Pau PastorFundació Docència i Recerca Mútua de Terrassa, Terrassa, Barcelona, Spain.
Jarod RutledgeWu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Hamilton OhWu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Edward N WilsonWu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Yann Le GuenWu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Rana R KhalidNCB, Quaid-i-Azam University, Islamabad, Pakistan.
Knight Alzheimer Disease Research Center (Knight ADRC)Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO 63110, USA.
Alzheimer Disease Neuroimaging Initiative (ADNI)
Fundació ACE Alzheimer Center Barcelona (FACE)
Barcelona-1
Stanford Alzheimer Disease Research Center (Stanford ADRC)
Chloe RobinsGenomic Sciences, GSK Pharma R&D, 1250 S Collegeville Rd., Collegeville, PA 19426, USA.
David J PulfordGenomic Sciences, GSK Pharma R&D, 1250 S Collegeville Rd., Collegeville, PA 19426, USA.
Rawan TarawnehThe University of New Mexico, Albuquerque, NM 87131, USA.
Laura IbanezDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Tony Wyss-CorayWu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Yun Ju SungDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA; Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO 63110, USA. Electronic address: cruchagac@wustl.edu.
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
$69.5MStanford 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
$28.7MIdentification 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
$3.5MSex-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
$2.7MGenetic Architecture of Alzheimer's disease ProteinopathiesR56AG064877 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CRUCHAGA, CARLOS, KAMBOH, M. ILYAS · 2019 to 2019
$2.6MGenetic Modifiers of TREM2 in Alzheimer's DiseaseR01AG058501 · NIA · WASHINGTON UNIVERSITY · PI Carlos Cruchaga · 2024 to 2026
$2.2MElucidating the Role of Endothelial Dysfunction in Alzheimer Disease: Towards A New Data-Driven Disease ModelRF1AG083744 · NIA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI TARAWNEH, RAWAN · 2023 to 2023
$2.1MNIA NIH HHS P01 AG003991NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066515NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG078964NIA NIH HHS R56 AG064877NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS RF1 AG083744NIA NIH HHS U01 AG024904NIMH NIH HHS T32 MH135853
Abstract
Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164 (57%) are novel. The identified proteins cluster in four different pseudo-trajectories groups spanning the AD continuum and were enriched in pathways including neuronal death, apoptosis, and tau phosphorylation (early stages), microglia dysregulation and endolysosomal dysfunction (mid stages), brain plasticity and longevity (mid stages), and microglia-neuron crosstalk (late stages). Using machine learning, we created and validated highly accurate and replicable (area under the curve [AUC] > 0.90) models that predict AD biomarker positivity and clinical status. These models can also identify people that will convert to AD.
Indexed as
Alzheimer DiseaseProteomicsAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersCohort StudiesFemaleHumansMachine LearningMaleMicrogliatau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer diseaseATNbiomarkersCSFdementia progressionmachine learningproteomicspseudo-trajectorySomaScan
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