ArticleNeuron2020
Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
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Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 333 papers, 1 of them a synthesis that pooled it.
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333citing papers in PubMed, 1 pooled it
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Who cites it
333 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Dissecting Detergent-Insoluble Proteome in Alzheimer's Disease by TMTc-Corrected Quantitative Mass Spectrometry.Molecular & cellular proteomics : MCP · 2023Pooled it
- Collagen Triple Helix Repeat Containing 1 (CTHRC1) in the Nervous System: Expression, Signaling Mechanisms, and Functional Implications.Journal of molecular neuroscience : MN · 2026Review
- Profiling of Aggregated Amyloid β42-induced Proteomic Alterations in KOLF2.1J Induced Pluripotent Stem Cell-derived Neurons.bioRxiv : the preprint server for biology · 2026Article
- Spatiotemporal characterization of Alzheimer disease pathology in living human brain tissue.Nature communications · 2026Article
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Deciphering the rules of regulated cell death subroutines by in silico methods.Journal of advanced research · 2026Review
- Genetic and pathway complexity in Alzheimer's disease: Insights from multi-omic data about the immune response and mitochondrial function.Neural regeneration research · 2026Article
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Integrated multi-omics analysis identifies potential therapeutic targets for Alzheimer's disease.Neural regeneration research · 2026Article
- UBA1 knockdown dysregulates UBA1-sensitive proteins and impairs muscle function in models of spinal muscular atrophy X-linked 2.Disease models & mechanisms · 2026Article
- Astrocytic lactate shuttle disruption and the energy-starved lysosome in Alzheimer's disease.Research square · 2026Article
- Patient cerebral organoids capture Alzheimer's disease proteomic biomarkers and drug targets.bioRxiv : the preprint server for biology · 2026Article
- Associations of stable psychological traits with multi-omic subtypes of Alzheimer's dementia.Translational psychiatry · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Phosphoproteomic profiling reveals post-translational dysregulation in Huntington's disease patient-derived neurons.Cellular & molecular biology letters · 2026Article
- Article
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- Overexpression of WNT3a in the Hippocampus Can Partly Alleviate Deficits in Animal Models of Alzheimer's Disease.Neurochemical research · 2026Article
- Gene Expression Analysis of Mitochondria-Associated Membrane (MAM)-Related Genes in ER Stress and Alzheimer's Disease.Cellular and molecular neurobiology · 2026Article
- Article
273 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
34 authors.
Bing BaiDepartments of Structural Biology and Developmental Neurobiology, 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. Electronic address: xusheng.wang@und.edu.
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.
Ping-Chung ChenDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Kaiwen YuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Kaushik Kumar DeyDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jay M YarbroDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Xian HanDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Brianna M LutzDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Shuquan RaoDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Yun JiaoDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jeffrey M SiffordDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jonghee HanDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Minghui WangDepartments of Psychiatry and Neuroscience, The Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY 10468, USA.
Haiyan TanCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Timothy I ShawCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Ji-Hoon ChoCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Suiping ZhouCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hong WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Mingming NiuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Ariana MancieriDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Kaitlynn A MesslerDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Xiaojun SunDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Zhiping WuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Vishwajeeth PagalaCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Anthony A HighCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Wenjian BiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hui ZhangDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hongbo ChiDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Vahram HaroutunianDepartments of Psychiatry and Neuroscience, The Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY 10468, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences and Department of Pharmacological Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ 85351, USA.
Gang YuDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Junmin PengDepartments 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. Electronic address: junmin.peng@stjude.org.
Funding
Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MVascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Charles B Hall · 1985 to 2026
$73.9MSUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5MIntegrative 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
$26.0MIntegrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6MTRANSGENIC MODELING OF TAUOPATHYP01AG017216 · NIA · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 1999 to 2011
$12.0MPREDICTORS OF THE RATE OF COGNITIVE DECLINE IN ELDERLY SUBJECTSP50AG025711 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI POTTER, HUNTINGTON · 2005 to 2010
$8.2MNational Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8MSystems 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
$6.3MNCI NIH HHS P30 CA021765NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG019610NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG047928NIA NIH HHS R01 AG053987NIA NIH HHS R01 AG057907NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG059319NIA NIH HHS RF1 AG064909NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046170NIGMS NIH HHS R01 GM114260NINDS NIH HHS R01 NS079796NINDS NIH HHS R01 NS080820NINDS NIH HHS U24 NS072026
Abstract
Alzheimer's disease (AD) displays a long asymptomatic stage before dementia. We characterize AD stage-associated molecular networks by profiling 14,513 proteins and 34,173 phosphosites in the human brain with mass spectrometry, highlighting 173 protein changes in 17 pathways. The altered proteins are validated in two independent cohorts, showing partial RNA dependency. Comparisons of brain tissue and cerebrospinal fluid proteomes reveal biomarker candidates. Combining with 5xFAD mouse analysis, we determine 15 Aβ-correlated proteins (e.g., MDK, NTN1, SMOC1, SLIT2, and HTRA1). 5xFAD shows a proteomic signature similar to symptomatic AD but exhibits activation of autophagy and interferon response and lacks human-specific deleterious events, such as downregulation of neurotrophic factors and synaptic proteins. Multi-omics integration prioritizes AD-related molecules and pathways, including amyloid cascade, inflammation, complement, WNT signaling, TGF-β and BMP signaling, lipid metabolism, iron homeostasis, and membrane transport. Some Aβ-correlated proteins are colocalized with amyloid plaques. Thus, the multilayer omics approach identifies protein networks during AD progression.
Indexed as
Disease ProgressionMetabolic Networks and PathwaysProteomicsAgedAged, 80 and overAlzheimer DiseaseAnimalsBiomarkersBrainFemaleHumansMaleMiceMice, Mutant StrainsMiddle AgedPhosphoproteinsBiomarkersPhosphoproteinsProteomeAlzheimer’s diseasebiomarkercerebrospinal fluidgenomicsmass spectrometrymulti-omicsphosphoproteomeproteomeproteomicssystems biology
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