ArticleNature medicine2020
Large-scale proteomic analysis of Alzheimer's disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation.
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In one paragraph
Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 640 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
640citing papers in PubMed, 1 pooled it
77.5field-weighted citation impact, top 1% of its field
What it found
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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.
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Who cites it
640 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,017 citations in OpenAlex.
- Pooled it
- Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Transcriptomic analysis reveals and validates lipid raft-associated biomarkers and functional networks in Alzheimer's disease.IBRO neuroscience reports · 2026Article
- Metabolic reprogramming of microglia: Effects on development, disease, and therapeutic potential.Neural regeneration research · 2026Article
- Exploratory bidirectional Mendelian randomisation analysis of cerebrospinal fluid metabolites associated with cerebral palsy and epilepsy.BMJ paediatrics open · 2026Article
- Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner.Nature neuroscience · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- AHA1 Regulates Aβ Production via Modulation of APP Abundance and γ-Secretase Assembly.Journal of neurochemistry · 2026Article
- A biphasic astrocytic PTGDS trajectory marks a metabolic vulnerability stage in prodromal Alzheimer's disease.Research square · 2026Article
- Neurofilament Light Chain (NfL) in Neurodegenerative Diseases: Biological and Clinical Significance, Multi-Omics Integration, and AI-Driven Biomarker Modeling for Precision Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains.Cell reports. Medicine · 2026Article
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Integrative multi-omics analysis of metabolite-protein interaction networks across different stages of coronary heart disease.Scientific reports · 2026Article
- CD44 as a Conserved Biomarker and Functional Modulator of Neuroinflammation in Multiple Sclerosis and Beyond.Molecular neurobiology · 2026Article
- hypeR-GEM: connecting metabolite signatures to enzyme-coding genes via genome-scale metabolic models.Bioinformatics (Oxford, England) · 2026Article
- Inhibition of Moesin and CD44 in stem cell-derived neurons affects the pathological genetic signature associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Functional and Transcriptional Downregulation of Glutamate Transporters (EAAT1 and EAAT2) via DNMT3B Overexpression in Glial Cells.Molecular neurobiology · 2026Article
- Human Stem Cell-Derived Neurospheroids and a Multi-Assay Strategy Provide Brain Cytotoxicity New Insights from ADB-FUBIATA Exposure.Neurotoxicity research · 2026Article
- Astrocytic lactate shuttle disruption and the energy-starved lysosome in Alzheimer's disease.Research square · 2026Article
580 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 16 institutions in 1 country.
Erik C B Johnson *Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA. erik.c.b.johnson@emory.edu.ORCID http://orcid.org/0000-0002-0604-2944
Eric B Dammer *Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-2947-7606
Duc M DuongGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.
Lingyan PingGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.
Maotian ZhouGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.
Luming YinDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Lenora A HigginbothamDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Andrew GuajardoJohns Hopkins School of Medicine, Baltimore, MD, USA.
Bartholomew WhiteJohns Hopkins School of Medicine, Baltimore, MD, USA.
Juan C TroncosoJohns Hopkins School of Medicine, Baltimore, MD, USA.
Madhav ThambisettyClinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Thomas J MontineDepartment of Pathology, School of Medicine, Stanford University, Palo Alto, CA, USA.
Edward B LeeCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4589-1180
John Q TrojanowskiCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9239-8794
Thomas G BeachDepartment of Pathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
Eric M ReimanBanner Alzheimer's Institute, Arizona State University and University of Arizona, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-0705-3696
Vahram HaroutunianDepartments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5860-2512
Minghui WangDepartment of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eric SchadtDepartment of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-7892-8808
Bin ZhangDepartment of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0001-7189-7917
Nilüfer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Todd E GoldeDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Vladislav A PetyukBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Philip L De JagerCenter for Translational & Computational Neuroimmunology, Department of Neurology, Taub Institute, Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, NY, USA.ORCID http://orcid.org/0000-0002-8057-2505
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Thomas S WingoGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-7679-6282
Srikant RangarajuDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-2765-1500
Ihab HajjarDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Joshua M ShulmanDepartments of Neurology, Neuroscience and Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
James J LahGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.
Allan I LeveyGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA. alevey@emory.edu.ORCID http://orcid.org/0000-0002-3153-502X
Nicholas T SeyfriedGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA. nseyfri@emory.edu.ORCID http://orcid.org/0000-0002-4507-624X
Emory University · USIcahn School of Medicine at Mount Sinai · USJohns Hopkins University · USUniversity of Pennsylvania · USBanner Sun Health Research Institute · USBaylor College of Medicine · USJames J. Peters VA Medical Center · USMayo Clinic in Florida · USNational Institutes of Health · USNewYork–Presbyterian Hospital · USPacific Northwest National Laboratory · USRush University Medical Center · USStanford University · USUniversity of Arizona · USUniversity of Florida · USWinnMed · US
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
$43.3M'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 1985 to 2019
$37.6MUPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DETRE, JOHN A · 1991 to 2020
$35.1MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3MThe Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI Amy D Rodriguez · 2020 to 2026
$29.0MIntegrative 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
$26.0MThe Emory Alzheimer's Disease CenterP50AG025688 · NIA · EMORY UNIVERSITY · PI WALKER, LARY C · 2005 to 2019
$25.7MIntegrating 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
$24.6MRISK 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
$13.7MBLRD VA I01 BX003853NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066511NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG025688NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG050631NIA NIH HHS R01 AG053960NIA NIH HHS R01 AG056533NIA NIH HHS R01 AG057339NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG057911NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG061796NIA NIH HHS R01 AG061800NIA NIH HHS R01 AG072120NIA NIH HHS R01 AG075827NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG051633NIA NIH HHS RF1 AG054014NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057470NIA NIH HHS RF1 AG057471NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG059319NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG061357NINDS NIH HHS K08 NS099474NINDS NIH HHS R01 NS114130NINDS NIH HHS U24 NS072026
Abstract
Our understanding of Alzheimer's disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly associated with AD pathology and cognitive impairment. This module was enriched in AD genetic risk factors and in microglia and astrocyte protein markers associated with an anti-inflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were elevated in cerebrospinal fluid in early stages of the disease. In this study of >2,000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brains that may serve as therapeutic targets and fluid biomarkers for the disease.
Indexed as
Energy MetabolismAlzheimer DiseaseAnimalsAstrocytesBiomarkersBrainCase-Control StudiesCerebrospinal FluidCohort StudiesDisease ProgressionFemaleGene Regulatory NetworksHumansMaleMass SpectrometryMetabolic Networks and PathwaysBiomarkersNerve Tissue Proteins
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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.