ArticleCell2025
Multiscale proteomic modeling reveals protein networks driving Alzheimer's disease pathogenesis.
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Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed.
- Integrative plasma proteomic network analysis identifies physical activity-associated protein modules potentially mediating type 2 diabetes risk.Cardiovascular diabetology · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Niche-Mediated Neural Priming Enables Robust and Scalable Generation of Human Choroid Plexus Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomic comparison of human neural cell-derived extracellular vesicles and parental cells from Alzheimer's disease and cognitively normal individuals.Science China. Life sciences · 2026Article
- Microglia in Alzheimer's Disease: From Homeostatic Guardians to Multifaceted Drivers of Neuropathology.Cells · 2026Review
- Review
- Patient cerebral organoids capture Alzheimer's disease proteomic biomarkers and drug targets.bioRxiv : the preprint server for biology · 2026Article
- High-Dimensional Sensitivity Analysis for Genomic Studies: An Adversarial Framework for Learning Worst-Case Latent Confounders.bioRxiv : the preprint server for biology · 2026Article
- Early, sex-dependent and progressive proteomic imbalance in the amygdala during Alzheimer´s disease continuum.Biology of sex differences · 2026Article
- In vivo profiling of astrocyte secretome reveals brain-region specific regulatory networks in a mouse model of amyloid pathology.Molecular neurodegeneration · 2026Article
- Article
- Intranasal Formaldehyde Exposure Induces RAGE-Mediated Alteration of the ADAM10/BACE1 Expression Balance and Amyloid Deposition.Biomedicines · 2026Article
- Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans.Aging cell · 2026Article
- Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Decoding Alzheimer's Disease One Cell Class at a Time.Cellular and molecular neurobiology · 2026Review
- Single Plaque Proteomics Reveals the Composition and Dynamics of the Amyloid Microenvironment in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Cell type-resolved proteomics reveals intra- and intercellular signaling in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- The tango of immune and neural cells: orchestrating neuroinflammation mediated brain disorders.Frontiers in immunology · 2026Review
- Efficacy and exploratory treatment-response modeling of acupuncture for acute migraine based on DIA proteomics: a study protocol for a randomized controlled trial.Frontiers in medicine · 2026Article
- NAD⁺ Reduction in Glutamatergic Neurons Induces Lipid Catabolism and Neuroinflammation in the Brain via SARM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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Authors and funding
29 authors.
Erming WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Kaiwen YuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Center for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jiqing CaoAlzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; Geriatric Research Education & Clinical Center (GRECC), Minneapolis VA Health Care System, Minneapolis, MN 55417, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Pavel KatselAlzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; MIRECC, Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, New York, NY 10468, USA.
Won-Min SongDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Zhen WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Yuxin LiDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Center for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Xusheng WangCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Qian WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Peng XuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Gefei YuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Li ZhuAlzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; Geriatric Research Education & Clinical Center (GRECC), Minneapolis VA Health Care System, Minneapolis, MN 55417, USA.
Jia GengDepartment of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; Geriatric Research Education & Clinical Center (GRECC), Minneapolis VA Health Care System, Minneapolis, MN 55417, USA.
Parnian HabibiDepartment of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA.
Lu QianDepartment of Pharmacology, Physiology & Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
Tony TuckDepartment of Pharmacology, Physiology & Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
Aiqun LiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Julia TcwDepartment of Pharmacology, Physiology & Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA; Bioinformatics Program, Boston University Faculty of Computing & Data Sciences, Boston, MA 02215, USA.
Panos RoussosDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Kristen J BrennandDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
Vahram HaroutunianAlzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; MIRECC, Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, New York, NY 10468, USA.
Erik C B JohnsonGoizueta Alzheimer's Disease Research Center, Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Nicholas T SeyfriedGoizueta Alzheimer's Disease Research Center, Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Allan I LeveyGoizueta Alzheimer's Disease Research Center, Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Junmin PengDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: junmin.peng@stjude.org.
Dongming CaiAlzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; MIRECC, Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, New York, NY 10468, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; Geriatric Research Education & Clinical Center (GRECC), Minneapolis VA Health Care System, Minneapolis, MN 55417, USA. Electronic address: cai00268@umn.edu.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: bin.zhang@mssm.edu.
Funding
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MIntegrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MSystems Approaches to Novel Molecular Mechanism in Alzheimer's DiseaseRF1AG064909 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI PENG, JUNMIN, YU, GANG · 2019 to 2024
$6.4MIntegrative Network Modeling of Cognitive Resilience to Alzheimer's DiseaseR01AG057907 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, HAROUTUNIAN, VAHRAM · 2017 to 2021
$6.3MSystems modeling of shared and distinct molecular mechanisms underlying comorbid Major Depressive Disorder and Alzheimer's diseaseR01AG062355 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, SALTON, STEPHEN R · 2018 to 2022
$4.7MIdentification 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
$4.5MNovel Network Biology Approaches to Reposition FDA-approved Drugs for Alzheimer's DiseaseR01AG068030 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER, CAI, DONGMING · 2020 to 2024
$4.2MBLRD VA I01 BX003380BLRD VA I01 BX005934NIAID NIH HHS R21 AI149013NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG048923NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG062355NIA NIH HHS R01 AG063819NIA NIH HHS R01 AG068030NIA NIH HHS R01 AG074010NIA NIH HHS R01 AG077828NIA NIH HHS R01 AG082362NIA NIH HHS R01 AG083941NIA NIH HHS R01 AG085182NIA NIH HHS R56 AG058655NIA NIH HHS RF1 AG048923NIA NIH HHS RF1 AG054014NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG062661NIA NIH HHS RF1 AG064909NIA NIH HHS RF1 AG074010NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG061356NIA NIH HHS UH2 AG083258NIDA NIH HHS R01 DA051191NIDCR NIH HHS R01 DE029322NINDS NIH HHS R01 NS145483
Abstract
The molecular mechanisms underlying the pathogenesis of Alzheimer's disease (AD), the most common form of dementia, remain poorly understood. Proteomics offers a crucial approach to elucidating AD pathogenesis, as alterations in protein expression are more directly linked to phenotypic outcomes than changes at the genetic or transcriptomic level. In this study, we develop multiscale proteomic network models for AD by integrating large-scale matched proteomic and genetic data from brain regions vulnerable to the disease. These models reveal detailed protein interaction structures and identify putative key driver proteins (KDPs) involved in AD progression. Notably, the network analysis uncovers an AD-associated subnetwork that captures glia-neuron interactions. AHNAK, a top KDP in this glia-neuron network, is experimentally validated in human induced pluripotent stem cell (iPSC)-based models of AD. This systematic identification of dysregulated protein regulatory networks and KDPs lays down a foundation for developing innovative therapeutic strategies for AD.
Indexed as
Alzheimer DiseaseAnimalsApolipoproteins EBrainDatasets as TopicGenotypeHumansInduced Pluripotent Stem CellsMiceNeurogliaNeuronsProtein Interaction MapsProteomeProteomicsApoE protein, humanApolipoproteins EProteomeAHNAKAlzheimer’s diseaseBayesian causal inference networkco-expression networkkey driver analysisproteomicstranscriptomics
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