Evidence map›Paper›PMID 41875888›Full record

ArticleCell2026

Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures.

Him K Shrestha, Huan Sun, Jay M Yarbro, DongGeun Lee, Danting Liu, Erming Wang, Meghan McReynolds, Nan Zhang, Boer Xie, Shu Yang and 37 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07516119 (Assessing Tools That Predict and Stage Mild Cognitive Impairment), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07516119 recruitingnot on this map

Assessing Tools That Predict and Stage Mild Cognitive Impairment

TypeobservationalSponsorPrevention Research Consortium Corp.Ran2026 to 2029Enrolled100ConditionsMild Cognitive Impairment (MCI), Alzheimer Dementia (AD), Alzheimer Disease (AD), APOE-4 Positive
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

47 authors.

Him K ShresthaDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Huan SunDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jay M YarbroDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
DongGeun LeeDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Danting LiuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Erming WangDepartment of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Genomics Institute, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Meghan McReynoldsDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nan ZhangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Boer XieDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Shu YangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kaiwen YuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Suresh PoudelCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Yuxin LiDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA; Center for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Zuo-Fei YuanCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Dehui KongDepartment of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Genomics Institute, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zhen WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Mingming NiuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Hong WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Masihuz ZamanDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Ju WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
David R VanderwallDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Yu SunDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Zhiping WuDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Ping-Chung ChenDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Bing BaiDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Anthony A HighCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Júlia FauraVIB-UAntwerp Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Chunyu LiuDepartment of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Erik C B JohnsonDepartment of Neurology, School of Medicine, Emory University, Atlanta, GA, USA.
Nicholas T SeyfriedDepartment of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA.
Allan I LeveyDepartment of Neurology, School of Medicine, Emory University, Atlanta, GA, USA.
Vahram HaroutunianDepartments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; James J. Peters VA Medical Center, Bronx, NY, USA.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, AZ, USA.
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
Michael DeTureDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Takahisa KanekiyoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Guojun BuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Pamela J McLeanDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Rosa RademakersVIB-UAntwerp Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. Electronic address: rosa.rademakers@uantwerpen.vib.be.
Gang YuDepartment of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: gang.yu@utsouthwestern.edu.
Xusheng WangCenter for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: xwang39@uthsc.edu.
Bin ZhangDepartment of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Genomics Institute, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: bin.zhang@mssm.edu.
Junmin PengDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: junmin.peng@stjude.org.

Funding

TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI ALLAN I LEVEY · 2019 to 2026
$69.7M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI ALISON M GOATE · 2021 to 2026
$42.0M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI ALIREZA ATRI · 2021 to 2026
$24.9M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Targeting CLEC-2/podoplanin as a therapeutic strategy for pancreatic cancerP20GM109024 · NIGMS · NORTH DAKOTA STATE UNIVERSITY · PI John Curlee Wilkinson · 2016 to 2026
$20.5M
Utilization of proteomics and lipidomics to identify modifiers of LBDU54NS110435 · NINDS · MAYO CLINIC JACKSONVILLE · PI MCLEAN, PAMELA J · 2019 to 2023
$14.5M
NIA NIH HHS K08 AG068604NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072980NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG047928NIA NIH HHS R01 AG053960NIA NIH HHS R01 AG053987NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG061800NIA NIH HHS R01 AG068581NIA NIH HHS R01 AG083981NIA NIH HHS R01 AG092468NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057470NIA NIH HHS RF1 AG057471NIA NIH HHS RF1 AG062181NIA NIH HHS RF1 AG064909NIA NIH HHS RF1 AG068581NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG061357NIA NIH HHS U19 AG069701NIA NIH HHS U54 AG065187NIGMS NIH HHS P20 GM109024NIMH NIH HHS R01 MH110920NINDS NIH HHS R35 NS097261NINDS NIH HHS U24 NS072026NINDS NIH HHS U54 NS110435
6 · The paper itself

Abstract

Neurodegenerative diseases (NDs) pose clinical challenges due to their complexity and molecular heterogeneity. Here, we present a pan-neurodegeneration atlas (PanNDA) from multilayer, deep proteomic analysis of 2,279 human brain samples spanning 6 major NDs: Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal lobar degeneration with TDP-43 pathology, progressive supranuclear palsy with tau pathology, vascular dementia, and Parkinson's disease. PanNDA integrates data from whole proteome, detergent-insoluble proteome, and posttranslational modifications (phosphorylation and ubiquitination), enabling intra- and inter-disease comparisons. Intra-disease analyses uncover distinct molecular subtypes (e.g., three in AD and four in LBD), reveal dysregulated pathways, and prioritize top-ranked proteins. Inter-disease comparisons identify shared alterations in NDs, such as GPNMB in microglial and lysosomal activation and NPTX2 in synaptic regulation, alongside disease-specific changes and hub regulators within protein networks. Overall, PanNDA provides a systems-level framework for understanding ND mechanisms and serves as a foundational resource that is accessible via an interactive website: https://penglab.shinyapps.io/pannda.

Indexed as

Neurodegenerative DiseasesProteomicsAlzheimer DiseaseBrainDementia, VascularFrontotemporal Lobar DegenerationHumansLewy Body DiseaseMembrane GlycoproteinsParkinson DiseaseProtein Processing, Post-TranslationalProteomeSupranuclear Palsy, ProgressiveGPNMB protein, humanMembrane GlycoproteinsProteomeAlzheimer's diseasefrontotemporal lobar degenerationLewy body dementiamass spectrometryneurodegenerative diseasesParkinson’s diseaseposttranslational modificationsprogressive supranuclear palsyproteomicsvascular dementia

Identifiers

PMID41875888
PMCPMC13014018

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.