Evidence map›Paper›PMID 31542321›Full record

ArticleNeuron2019

Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis.

Peter Dongmin Sohn, Cindy Tzu-Ling Huang, Rui Yan, Li Fan, Tara E Tracy, Carolina M Camargo, Kelly M Montgomery, Taylor Arhar, Sue-Ann Mok, Rebecca Freilich and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 1% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.

  1. Pooled it
  2. Review
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  14. Impaired AIS plasticity in ankyrin-G mutant mice alters cortical excitability and behavior.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Article
  16. Multi-omic phenotyping of iPSC-derived neurons harboring thebioRxiv : the preprint server for biology · 2025
    Article
  17. Article
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  19. Review
  20. Article

37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 2 countries.

Peter Dongmin SohnGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Cindy Tzu-Ling HuangGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Rui YanDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Li FanHelen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medical Center, New York, NY10021, USA.
Tara E TracyGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Carolina M CamargoNeuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Kelly M MontgomeryDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Taylor ArharDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Sue-Ann MokDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Rebecca FreilichDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Justin BaikDepartment of Physics, University of California, Berkeley, Berkeley, CA 94720, USA.
Manni HeDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Shiaoching GongHelen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medical Center, New York, NY10021, USA.
Erik D RobersonDepartments of Neurology and Neurobiology, University of Alabama, Birmingham, Birmingham, AL 35294, USA.
Celeste M KarchDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jason E GestwickiDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Ke XuDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Kenneth S KosikNeuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Li GanGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: lig2033@med.cornell.edu.
University of California, San Francisco · USUniversity of California, Berkeley · USCornell University · USGladstone Institutes · USUniversity of California, Santa Barbara · USUniversity of Alabama at Birmingham · USUniversity of Alberta · CAWashington University in St. Louis · US

Funding

Project 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CUERVO, ANA MARIA · 2016 to 2020
$10.8M
Molecular Chaperones and Small MoleculesR01NS059690 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason E Gestwicki · 2008 to 2026
$7.9M
RESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGYT32GM064337 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2002 to 2021
$7.8M
Functional characterization of Alzheimer's disease associated genetic variantsR01AG057497 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAN, LI, SHEN, YIN · 2017 to 2021
$4.2M
Tau acetylation in Alzheimer's diseaseR01AG054214 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2017 to 2021
$3.3M
Molecular mechanisms in progranulin deficient frontotemporal dementiaR01AG051390 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2015 to 2019
$2.5M
EXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1M
Synaptic mechanisms of tau-mediated pathogenesis in human iPSC-derived neuronsK01AG057862 · NIA · J. DAVID GLADSTONE INSTITUTES · PI TRACY, TARA · 2018 to 2022
$626k
GENETIC DISRUPTION OF TAU METABOLISM IN TAUOPATHIESK01AG046374 · NIA · WASHINGTON UNIVERSITY · PI KARCH, CELESTE MARIE · 2014 to 2018
$568k
NCRR NIH HHS C06 RR018928NIA NIH HHS K01 AG046374NIA NIH HHS K01 AG057862NIA NIH HHS R01 AG051390NIA NIH HHS R01 AG054214NIA NIH HHS R01 AG057497NIGMS NIH HHS T32 GM064337NINDS NIH HHS R01 NS059690NINDS NIH HHS U54 NS100717
6 · The paper itself

Abstract

Dysregulation of neuronal excitability underlies the pathogenesis of tauopathies, including frontotemporal dementia (FTD) with tau inclusions. A majority of FTD-causing tau mutations are located in the microtubule-binding domain, but how these mutations alter neuronal excitability is largely unknown. Here, using CRISPR/Cas9-based gene editing in human pluripotent stem cell (iPSC)-derived neurons and isogenic controls, we show that the FTD-causing V337M tau mutation impairs activity-dependent plasticity of the cytoskeleton in the axon initial segment (AIS). Extracellular recordings by multi-electrode arrays (MEAs) revealed that the V337M tau mutation in human neurons leads to an abnormal increase in neuronal activity in response to chronic depolarization. Stochastic optical reconstruction microscopy of human neurons with this mutation showed that AIS plasticity is impaired by the abnormal accumulation of end-binding protein 3 (EB3) in the AIS submembrane region. These findings expand our understanding of how FTD-causing tau mutations dysregulate components of the neuronal cytoskeleton, leading to network dysfunction.

Indexed as

Axon Initial SegmentCytoskeletonElectrophysiological PhenomenaExtracellular SpaceFrontotemporal DementiaHomeostasisHumansInduced Pluripotent Stem CellsMicrotubule-Associated ProteinsMutationNeuronal PlasticityNeuronsProtein Aggregation, Pathologicaltau ProteinsMAPRE3 protein, humanMAPT protein, humanMicrotubule-Associated Proteinstau Proteinsaxon initial segmentcytoskeletonEB3FTDhomeostasisneuronal activitytau

Identifiers

PMID31542321
PMCPMC6880876
OpenAlexW2973501556

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.