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41/100

✓ Peer-reviewed alzhub usefulness score 41 out of 100. Inflammation and the immune system

Topic: Brain proteins, microglia and lab models

Abstract Background Glial reactivity has a major role in Alzheimer's disease (AD) etiology and progression, with astrocytes and microglia orchestrating neuroinflammatory responses. Even though experimental evidence indicate that activated microglia can induce astrocyte reactivity, it remains to be elucidated whether microglia activation influences amyloid‐β (Aβ) effects on astrocyte reactivity in the living AD human brain. Using imaging and fluid biomarker data in individuals across the aging and AD clinical spectrum, we tested the hypothesis that microglia influence the effects of Aβ pathology on astrocyte reactivity. Method Data was obtained from the Translational Biomarkers in Aging and Dementia (TRIAD) study. We studied 62 cognitively unimpaired (CU), 26 mild cognitive impairment (MCI), and 13 AD dementia participants who had positron emission tomography (PET) data for TSPO microglial activation ([ 11 C]PBR28) and Aβ plaques ([ 18 F]AZD4694), as well as reactive astrocyte marker plasma glial fibrillary acidic protein (GFAP). We further assessed tau phosphorylation with plasma phosphorylated tau at threonine 217 ( p ‐tau217) and tau aggregation with [ 18 F]MK‐6240 tau tangle PET. Additionally, a subset of 68 CU and 33 MCI individuals from the TRIAD cohort were evaluated with cerebrospinal fluid (CSF) microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2), [ 18 F]AZD4694 Aβ PET, and plasma GFAP. Result Regression analyses revealed that Aβ pathology was associated with astrocyte reactivity only in the presence of elevated levels of microglial activation, supporting that microglial activation influences Aβ effects on astrocyte reactivity. Similar results were observed when using TSPO PET and CSF sTREM2 to assess microglial activation (Figure 1). We also found that microglial activation and astrocyte reactivity were jointly associated with tau phosphorylation and aggregation (Figure 2). Importantly, the microglial‐dependent impact of Aβ on astrocyte reactivity contributed to cognitive impairment through tau pathology (Figure 3). Conclusion Our results suggest that microglial activation is a major phenomenon linking Aβ and astrocyte reactivity in the living AD brain. These findings help to elucidate the intricate crosstalk between microglia and astrocytes in the AD brain, offering insights for the development of glia‐targeting therapies.

Key findings

Even though experimental evidence indicate that activated microglia can induce astrocyte reactivity, it remains to be elucidated whether microglia activation influences amyloid‐β (Aβ) effects on astrocyte reactivity in the living AD human brain.
Result Regression analyses revealed that Aβ pathology was associated with astrocyte reactivity only in the presence of elevated levels of microglial activation, supporting that microglial activation influences Aβ effects on astrocyte reactivity.
Similar results were observed when using TSPO PET and CSF sTREM2 to assess microglial activation (Figure 1).
We also found that microglial activation and astrocyte reactivity were jointly associated with tau phosphorylation and aggregation (Figure 2).
Conclusion Our results suggest that microglial activation is a major phenomenon linking Aβ and astrocyte reactivity in the living AD brain.

Why it matters

In people across the aging and Alzheimer's clinical spectrum, amyloid pathology was associated with astrocyte reactivity only when microglial activation was also elevated. This supports microglia as a factor in how amyloid affects astrocytes, but it does not test or establish any treatment.

Study details

Participants62
Evidence strengthModerate

How this study scored 41/100

Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Alzheimer s & Dementia)
Journal's citation record	2 / 4	Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
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	4 / 5	2025 — within 3 year(s) of the newest study here
Sample size	1 / 4	62 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	1 / 7	Cited 1 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.3 citations a year over 3 year(s) since 2025
Impact for its field and year	1 / 6	Cited 0.3× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 1 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	1 / 3	University of Pittsburgh: institution h-index 1,470 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 9 institution(s) in 4 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41449556)
Free to read	2 / 2	Free to read
Total	41 / 100	—

What each of these 20 components measures, and what this score is not →

Read the original

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.

APA 7th

Ferrari‐Souza, J. P., Povala, G., Rahmouni, N., Bellaver, B., Ferreira, P. C., Leffa, D. T., et al. (2025). Microglia as a key player in Aβ‐related astrocyte reactivity. Alzheimer s & Dementia. https://doi.org/10.1002/alz70856_102677

Vancouver

Ferrari‐Souza JP, Povala G, Rahmouni N, Bellaver B, Ferreira PC, Leffa DT, et al. Microglia as a key player in Aβ‐related astrocyte reactivity. Alzheimer s & Dementia. 2025. doi:10.1002/alz70856_102677. PMID: 41449556.

BibTeX

@article{ferrarisouza2025-41449556,
  author  = {Ferrari‐Souza, João Pedro and Povala, Guilherme and Rahmouni, Nesrine and Bellaver, Bruna and Ferreira, Pâmela C.L. and Leffa, Douglas Teixeira and Lussier, Firoza Zubeida and Aguzzoli, Cristiano Schaffer and others},
  title   = {{Microglia as a key player in Aβ‐related astrocyte reactivity}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz70856_102677},
  pmid    = {41449556},
  url     = {https://doi.org/10.1002/alz70856_102677}
}

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