Evidence map›Paper›PMID 41268790›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Human microglia differentially respond to β-amyloid, tau, and combined Alzheimer's disease pathologies in vivo.

Morgan A Coburn, Ghazaleh Eskandari-Sedighi, Jonathan Hasselmann, Whitney England, Sepideh Kiani Shabestari, Kimiya Mansour, Amanda McQuade, Michael Armen Mgerian, Jean Paul Chadarevian, Christina Tu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. 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
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

16 authors.

Morgan A CoburnDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Ghazaleh Eskandari-SedighiSue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA.
Jonathan HasselmannDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Whitney EnglandDepartment of Pharmaceutical Sciences, University of California, Irvine, California, USA.
Sepideh Kiani ShabestariDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Kimiya MansourSue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA.
Amanda McQuadeDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Michael Armen MgerianInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
Jean Paul ChadarevianDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Christina TuSue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA.
Jorge SilvaSue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA.
Jaclyn BeckDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Zahara KeulenDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.
Robert C SpitaleDepartment of Pharmaceutical Sciences, University of California, Irvine, California, USA.
Hayk DavtyanSue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA.
Mathew Blurton-JonesDepartment of Neurobiology and Behavior, University of California, Irvine, California, USA.ORCID 0000-0002-7770-7157

Funding

Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI JUNMIN PENG · 2021 to 2026
$42.0M
Training in the Neurobiology of Aging and Alzheimers DiseaseT32AG000096 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI VIVEK SWARUP, Craig E Stark · 1985 to 2026
$9.6M
Training Program in Stem Cell Translational Medicine for Neurological DisordersT32NS082174 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PETER John DONOVAN, Leslie Michels Thompson · 2013 to 2026
$3.3M
Using human iPSC derived microglia and chimeric models to examine the role of PLCG2 in Alzheimers diseaseR01AG061895 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVTYAN, HAYK · 2018 to 2022
$2.9M
Examining the role of adaptive immunity in Alzheimer's Disease pathogenesisRF1AG055524 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2017
$2.7M
Training in Translational ADRD Neuroscience (TITAN)T32AG073088 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Joshua Grill, Elizabeth Head · 2021 to 2026
$2.2M
A novel platform for the investigation of human microgliaRF1DA048813 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK, GANDHI, SUNIL · 2019 to 2021
$2.1M
Manipulating DNA repair enzymes to examine the interactions between aging and Alzheimers disease with iPSC-derived microgliaR01AG056303 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2021
$1.9M
High-Throughput DNA SequencerS10OD021718 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2016 to 2016
$600k
PacBio RS Single Molecule, Real-Time (SMRT) DNA SequencerS10OD010794 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2012 to 2012
$600k
High Throughput DNA SequencerS10RR025496 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2009 to 2009
$500k
Alzheimer's Association ADSF-21-829655-CAlzheimer Society of Canada Discovery23-10BrightFocus Postdoctoral Fellowship Program in Alzheimer's A2025007FCure Alzheimer's FundNCI NIH HHS P30CA-062203NCRR NIH HHS 1S10RR025496-01NCRR NIH HHS S10 RR025496NIA NIH HHS R01 AG056303NIA NIH HHS R01 AG061895NIA NIH HHS RF1 AG055524NIA NIH HHS T32 AG000096NIA NIH HHS T32 AG073088NIA NIH HHS U19 AG069701NIDA NIH HHS RF1 DA048813NIH 2024-A-023-FELNIH HHS 1S10OD010794-01NIH HHS 1S10OD021718-01NIH HHS S10 OD010794NIH HHS S10 OD021718NIH Training Grant AG000096NIH Training Grant NS082174NINDS NIH HHS T32 NS082174Susan Scott FoundationThe Larry L. Hillblom Foundation : 2024-A-023-FEL and 2025-A-175-FEL
6 · The paper itself

Abstract

introductionRecent studies have identified important species-dependent differences in the response of microglia to β-amyloid (Aβ) pathology. Yet, whether human microglia also interact differently with the pathognomonic combination of amyloid and tau pathologies that occur in Alzheimer's disease (AD) remains unclear.

methodsWe generated a xenotolerant mouse model of AD that develops both plaque and tangle pathologies, transplanted stem cell-derived microglial progenitors and examined the interactions between human microglia and AD pathologies with scRNA sequencing, immunohistochemistry, and in vitro modeling.

resultsThe combined amyloid and tau pathologies induced robust type-I interferon and proinflammatory cytokine responses, as well as an increased adoption of a distinct "rod" morphology in human microglia. The rod morphology could be induced with type-I interferon treatment in vitro. DISCUSSION: We provide new insights into human microglial responses to combined AD pathologies and a novel platform to investigate and manipulate human microglia in vivo. HIGHLIGHTS: Amyloid pathology promotes the rapid development of neurofibrillary tangles and neuronal loss in a novel chimeric model of AD. Combined Alzheimer's disease pathologies lead to an expansion of disease-associated microglia (DAM) and exacerbate Interferon-responsive and cytokine/chemokine-enriched states in xenotransplanted human microglia. The combination of amyloid and tau promotes the development of a distinctive rod microglial phenotype that closely correlates with tau pathology and neurodegeneration. Rod morphology and transcriptional changes can be modeled in vitro by treatment of induced pluripotent stem cells (iPSC) -microglia with type-I interferons.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesMicrogliatau ProteinsAnimalsDisease Models, AnimalHumansMiceMice, TransgenicNeurofibrillary TanglesPlaque, AmyloidAmyloid beta-Peptidestau ProteinsAlzheimer's diseaseamyloid betahuman microgliaiPSCrod microgliatautype I interferon

Identifiers

PMID41268790
PMCPMC12635866

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.