ArticleCell2022
Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 2 of them syntheses that pooled it.
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214citing papers in PubMed, 2 pooled it
34.4field-weighted citation impact, top 1% of its field
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Who cites it
214 citing papers in PubMed, 2 syntheses or guidelines pooled it, 310 citations in OpenAlex.
- Mitochondrial dysfunction gene expression, DNA methylation, and inflammatory cytokines interaction activate Alzheimer's disease: a multi-omics Mendelian randomization study.Journal of translational medicine · 2024Pooled it
- Research trends and hotspots for frontotemporal dementia from 2000 to 2022: a bibliometric analysis.Frontiers in neurology · 2024Pooled it
- Elevation of the mechanically-sensitive e protein emerin links nuclear mechanotransduction to tau-induced cytoskeletal remodeling in neurons.Nucleus (Austin, Tex.) · 2026Article
- Alzheimer's disease target and drug discovery by leveraging multiomics and electronic health data.Nature neuroscience · 2026Article
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Oxidative stress and inflammation in neurodegenerative disorders.Archives of toxicology · 2026Review
- Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.Neural regeneration research · 2026Article
- Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Article
- APEX-seq maps transcriptome-wide subcellular RNA localization in living cells.Nature protocols · 2026Review
- The Interactions of Tau, RNA, and Stress Granules in Neurodegenerative Disease: A Comprehensive Review.Cells · 2026Review
- Metal Binding to Tau Protein: Physiological and Pathological Relevance.Biochemistry · 2026Review
- Article
- Tau pathology in epilepsy: emerging mechanisms and translational opportunities.Brain : a journal of neurology · 2026Review
- Tau protein as a regulator of mitochondrial function and dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ThebioRxiv : the preprint server for biology · 2026Article
- Microglial mitochondria transfer to astrocytes via GPNMB-enriched extracellular vesicles alleviates cognitive deficits in tauopathy mice.Nature neuroscience · 2026Article
- Selective knockout of PKA regulatory subunits reveal opposite catalytic and metabolic consequences with implications for Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
154 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 8 institutions in 2 countries.
Tara E TracyGladstone Institutes, San Francisco, CA 94158, USA; Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: ttracy@buckinstitute.org.
Jesus Madero-PérezHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: jem4002@med.cornell.edu.
Danielle L SwaneyGladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: danielle.swaney@gladstone.ucsf.edu.
Timothy S ChangDepartment of Neurology, Movement Disorders Program and Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Michelle MoritzDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Csaba KonradFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Michael E WardGladstone Institutes, San Francisco, CA 94158, USA.
Erica StevensonGladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.
Ruth HüttenhainGladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.
Grant KauweBuck Institute for Research on Aging, Novato, CA 94945, USA.
Maria MercedesHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Lauren Sweetland-MartinHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Xu ChenGladstone Institutes, San Francisco, CA 94158, USA.
Sue-Ann MokDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Man Ying WongHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Maria TelpoukhovskaiaGladstone Institutes, San Francisco, CA 94158, USA.
Sang-Won MinGladstone Institutes, San Francisco, CA 94158, USA.
Chao WangGladstone Institutes, San Francisco, CA 94158, USA.
Peter Dongmin SohnGladstone Institutes, San Francisco, CA 94158, USA.
Jordie MartinGladstone Institutes, San Francisco, CA 94158, USA.
Yungui ZhouGladstone Institutes, San Francisco, CA 94158, USA.
Wenjie LuoHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
John Q TrojanowskiCenter for Neurodegenerative Disease Research, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Virginia M Y LeeCenter for Neurodegenerative Disease Research, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shiaoching GongHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Giovanni ManfrediFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Giovanni CoppolaDepartment of Neurology, Movement Disorders Program and Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, USA.
Nevan J KroganGladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.
Daniel H GeschwindDepartment of Neurology, Movement Disorders Program and Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute of Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Li GanHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: lig2033@med.cornell.edu.
Gladstone Institutes · USCornell University · USQB3 · USUniversity of California, Los Angeles · USUniversity of Pennsylvania · USBuck Institute for Research on Aging · USUniversity of Alberta · CAUniversity of California, San Francisco · US
Funding
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI ALEXANDER, GENE E · 2001 to 2020
$32.5MMechanisms of inherited neurodegenerative diseasesZIANS003155 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI WARD, MICHAEL · 2016 to 2025
$24.7MProject 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2016 to 2020
$10.8MNational Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8MMaladaptive antiviral pathways in Alzheimer's diseaseR01AG072758 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2021 to 2025
$4.1MTau acetylation in Alzheimer's diseaseR01AG054214 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2017 to 2021
$3.3MTranslational Neuroscience Training GrantR25NS065723 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARMICHAEL, STANLEY THOMAS · 2009 to 2023
$2.8MEssential roles of DAP12 in tau metabolism and inflammation in Alzheimer's diseaseR01AG064239 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI LUO, WENJIE · 2020 to 2024
$2.1MUCLA Neuroscience Physician-Scientist Training ProgramUE5NS065723 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Stanley Thomas Carmichael, Jason D Hinman · 2024 to 2026
$1.2MSynaptic mechanisms of tau-mediated pathogenesis in human iPSC-derived neuronsK01AG057862 · NIA · J. DAVID GLADSTONE INSTITUTES · PI TRACY, TARA · 2018 to 2022
$626kNIA NIH HHS K01 AG057862NIA NIH HHS P30 AG019610NIA NIH HHS R01 AG054214NIA NIH HHS R01 AG064239NIA NIH HHS R01 AG072758NINDS NIH HHS R25 NS065723NINDS NIH HHS U24 NS072026NINDS NIH HHS U54 NS100717NINDS NIH HHS UE5 NS065723
Abstract
Tau (MAPT) drives neuronal dysfunction in Alzheimer disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize Tau interactomes modified by neuronal activity and mutations that cause frontotemporal dementia (FTD) in human induced pluripotent stem cell (iPSC)-derived neurons. We established interactions of Tau with presynaptic vesicle proteins during activity-dependent Tau secretion and mapped the Tau-binding sites to the cytosolic domains of integral synaptic vesicle proteins. We showed that FTD mutations impair bioenergetics and markedly diminished Tau's interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity. These multimodal and dynamic Tau interactomes with exquisite spatial resolution shed light on Tau's role in neuronal function and disease and highlight potential therapeutic targets to block Tau-mediated pathogenesis.
Indexed as
Protein Interaction MapsAlzheimer DiseaseAmino AcidsBiotinylationBrainCell NucleusDisease ProgressionEnergy MetabolismFrontotemporal DementiaHumansInduced Pluripotent Stem CellsMitochondriaMutant ProteinsMutationNerve DegenerationNeuronsAmino AcidsMutant Proteinstau Proteinsaffinity purification mass spectrometryAPEXinteractomemitochondrianeurodegenerationprotein-protein interactionsynapseTautauopathiesTau secretion
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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 OpenQuestion graph.