Evidence map›Paper›PMID 33207193›Full record

ArticleCell reports2020

Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression.

Jessica E Rexach, Damon Polioudakis, Anna Yin, Vivek Swarup, Timothy S Chang, Tam Nguyen, Arjun Sarkar, Lawrence Chen, Jerry Huang, Li-Chun Lin and 4 more

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

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Human microglia differentially respond to β-amyloid, tau, and combined Alzheimer's disease pathologies in vivo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  10. Article
  11. Article
  12. Entwined processes in Alzheimer's disease: Brain cellular senescence and Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Immune modulation to treat Alzheimer's disease.Molecular neurodegeneration · 2025
    Review
  17. Article
  18. Review
  19. Review
  20. Article

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

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

14 authors at 4 institutions in 2 countries.

Jessica E RexachProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Damon PolioudakisProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Anna YinProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Vivek SwarupProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Timothy S ChangProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tam NguyenProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Arjun SarkarProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Lawrence ChenProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jerry HuangProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Li-Chun LinDepartment of Pathology, University of California, San Francisco, San Francisco, CA, USA.
William SeeleyDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
John Q TrojanowskiDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dheeraj MalhotraNeuroscience and Rare Diseases, Roche Pharma Research and Early Development, F. Hoffman-LaRoche, Basel, Switzerland.
Daniel H GeschwindProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 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. Electronic address: dhg@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of California, San Francisco · USRoche (Switzerland) · CHUniversity of Pennsylvania · US

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Medicinal Chemistry CoreU19NS110456 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI ROBERT H MACH · 2019 to 2026
$44.1M
Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, YADONG · 2004 to 2018
$27.1M
Project IV "Tackling Heterogeneity of Cognitive Trajectory in LBD"U19AG062418 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 2019 to 2023
$18.1M
UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUSAN Y BOOKHEIMER · 2020 to 2026
$9.6M
Impact of coding and non-coding variation in progressive supranuclear palsyUG3NS104095 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DICKSON, DENNIS WILLIAM, GESCHWIND, DANIEL H · 2017 to 2019
$3.6M
Translational Neuroscience Training GrantR25NS065723 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARMICHAEL, STANLEY THOMAS · 2009 to 2023
$2.8M
Impact of coding and non-coding variation in progressive supranuclear palsyUH3NS104095 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DICKSON, DENNIS WILLIAM, GESCHWIND, DANIEL H · 2020 to 2021
$2.5M
UCLA Neuroscience Physician-Scientist Training ProgramUE5NS065723 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Stanley Thomas Carmichael, Jason D Hinman · 2024 to 2026
$1.2M
Single cell and tissue level functional genomic analysis of astrocyte-related mechanisms in tauopathyK08NS105916 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REXACH, JESSICA E · 2019 to 2023
$1.1M
UCLA ALZHEIMERS DISEASE CENTERP30AG010123 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEUCHTER, ANDREW · 1991 to 1998
–
NIA NIH HHS P01 AG017586NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG010123NIA NIH HHS P50 AG023501NIA NIH HHS U19 AG062418NICHD NIH HHS P50 HD103557NINDS NIH HHS K08 NS105916NINDS NIH HHS R25 NS065723NINDS NIH HHS U19 NS110456NINDS NIH HHS UE5 NS065723NINDS NIH HHS UG3 NS104095NINDS NIH HHS UH3 NS104095
6 · The paper itself

Abstract

To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia and bulk tissue from mouse and human AD, FTD, and PSP. We uncover a complex temporal trajectory of microglial-immune pathways involving the type 1 interferon response associated with tau pathology in the early stages, followed by later signatures of partial immune suppression and, subsequently, the type 2 interferon response. We find that genetic risk for dementias shows disease-specific patterns of pathway enrichment. We identify drivers of two gene co-expression modules conserved from mouse to human, representing competing arms of microglial-immune activation (NAct) and suppression (NSupp) in neurodegeneration. We validate our findings by using chemogenetics, experimental perturbation data, and single-cell sequencing in post-mortem brains. Our results refine the understanding of stage- and disease-specific microglial responses, implicate microglial viral defense pathways in dementia pathophysiology, and highlight therapeutic windows.

Indexed as

AgedAnimalsBrainDementiaFemaleFrontotemporal DementiaGene Regulatory NetworksGenetic Predisposition to DiseaseGenomicsHumansImmunosuppression TherapyInflammationMaleMiceMice, Inbred C57BLMicrogliatau Proteinschemical genomicsfrontotemporal dementiagene networkinflammasomeinterferonneurodegenerationprogressive supranuclear palsysystems biologytranscriptomics

Identifiers

PMID33207193
PMCPMC7842189
OpenAlexW3098926190

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.