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Record W4415954575 · doi:10.1038/s41593-025-02103-0

Microglia modulate Aβ-dependent astrocyte reactivity in Alzheimer’s disease

2025· article· en· W4415954575 on OpenAlexafffund
João Pedro Ferrari‐Souza, Guilherme Povala, Nesrine Rahmouni, Bruna Bellaver, Pâmela C.L. Ferreira, Marco Antônio De Bastiani, Douglas Teixeira Leffa, Firoza Z Lussier, Cristiano Schaffer Aguzzoli, Wagner S. Brum, Giovanna Carello‐Collar, Wyllians Vendramini Borelli, Joseph Therriault, Arthur C. Macedo, Stijn Servaes, Jenna Stevenson, Ilaria Pola, Serge Gauthier, Diogo O. Souza, Lucas Porcello Schilling, Mychael V. Lourenco, Gallen Triana‐Baltzer, Hartmuth C. Kolb, Andréa L. Benedet, Nicholas J. Ashton, Dana Tudorascu, Henrik Zetterberg, Kaj Blennow, Sterling C. Johnson, Tharick A. Pascoal, Pedro Rosa‐Neto, Eduardo R. Zimmer

Bibliographic record

VenueNature Neuroscience · 2025
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Institutes of HealthVetenskapsrådetUK Dementia Research InstituteNational Institute for Health and Care ResearchWeston Brain InstituteMcGill UniversityStiftelsen för Gamla TjänarinnorUniversity College London
KeywordsAstrocyteMicrogliaAstrogliosisGlial fibrillary acidic proteinGliosisPhosphorylationNeurogliaCentral nervous system

Abstract

fetched live from OpenAlex

Experimental evidence suggests that activated microglia induce astrocyte reactivity in neurodegenerative disorders, such as Alzheimer’s disease (AD). In this study, we investigated the association between microglial activation and amyloid-β (Aβ) with reactive astrogliosis in individuals across the AD spectrum. We examined 101 individuals using positron emission tomography radiotracers to assess Aβ deposition ([18F]AZD4694), tau aggregation ([18F]MK-6240) and microglial activation ([11C]PBR28), along with plasma biomarkers for astrocyte reactivity (GFAP) and tau phosphorylation (p-tau217). We further evaluated 251 individuals with cerebrospinal fluid levels of the microglial marker sTREM2. We found that Aβ pathology was associated with astrocyte reactivity across cortical brain regions only in the presence of microglial activation. The microglia-dependent effects of Aβ on astrocyte reactivity were further related to cognitive impairment through tau phosphorylation and aggregation. Our results suggest that microglial activation plays a key role in Aβ-related astrocyte reactivity, which, in turn, contributes to downstream pathological features of AD. Microglia influence amyloid-β effects on astrocyte reactivity in the living brain of individuals with Alzheimer’s disease. This phenomenon further contributes to cognitive impairment via tau phosphorylation and aggregation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.024
GPT teacher head0.297
Teacher spread0.273 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations18
Published2025
Admission routes2
Has abstractyes

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