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Microglia modulate Aβ-dependent astrocyte reactivity in Alzheimer's disease
Ferrari-Souza JP, Povala G, Rahmouni N, Bellaver B, Ferreira PCL, De Bastiani MA, Leffa DT, Lussier FZ, Aguzzoli CS, Brum WS, Carello-Collar G, Borelli WV, et al.. Nature Neuroscience, 2025-11-06
Topic: Amyloid, tau and blood-test diagnosis
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 ([ 18 F]AZD4694), tau aggregation ([ 18 F]MK-6240) and microglial activation ([ 11 C]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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ferrari-Souza, J. P., Povala, G., Rahmouni, N., Bellaver, B., Ferreira, P. C. L., De Bastiani, M. A., et al. (2026). Microglia modulate Aβ-dependent astrocyte reactivity in Alzheimer's disease. Nature Neuroscience. https://doi.org/10.1038/s41593-025-02103-0
Vancouver
Ferrari-Souza JP, Povala G, Rahmouni N, Bellaver B, Ferreira PCL, De Bastiani MA, et al. Microglia modulate Aβ-dependent astrocyte reactivity in Alzheimer's disease. Nature Neuroscience. 2026. doi:10.1038/s41593-025-02103-0. PMID: 41198899.
BibTeX
@article{ferrarisouza2026-41198899,
author = {Ferrari-Souza, J. P. and Povala, G. and Rahmouni, N. and Bellaver, B. and Ferreira, P. C. L. and De Bastiani, M. A. and Leffa, D. T. and Lussier, F. Z. and Aguzzoli, C. S. and Brum, W. S. and Carello-Collar, G. and Borelli, W. V. and others},
title = {{Microglia modulate Aβ-dependent astrocyte reactivity in Alzheimer's disease}},
journal = {Nature Neuroscience},
year = {2026},
doi = {10.1038/s41593-025-02103-0},
pmid = {41198899},
url = {https://doi.org/10.1038/s41593-025-02103-0}
}
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Key findings
- Experimental evidence suggests that activated microglia induce astrocyte reactivity in neurodegenerative disorders, such as Alzheimer's disease (AD).
- We found that Aβ pathology was associated with astrocyte reactivity across cortical brain regions only in the presence of microglial activation.
- 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.
Why it matters
Across 101 individuals studied with PET and plasma biomarkers, amyloid-beta pathology was associated with astrocyte reactivity only in the presence of microglial activation, and these effects related to cognitive impairment through tau phosphorylation and aggregation. This describes a pathway linking microglial activation, astrocytes and tau in the disease process, without testing any treatment, cure or prevention.
Study details
- Study designcohort
- Participants352
- Evidence strengthModerate
Limitations
TRIAD and WRAP participants are volunteers motivated to join dementia research, so self-selection may limit generalisability; TSPO PET, CSF sTREM2 and plasma GFAP capture only some glial phenotypes; TSPO is also expressed by astrocytes and endothelial cells and it is debated whether the signal reflects microglial activation or density.
How this study scored 66/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 65 of the 98 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Neuroscience) |
| Journal's citation record | 4 / 4 | Nature Neuroscience: journal h-index 593 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 352 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 35 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 10.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Eduardo Rigon Zimmer: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 24 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41198899) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 65 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 65 of the 98 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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