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Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease
Wellydo Kesllowd Marinho Escarião, Guilherme Henrique Silva, Hellen Suzane Clemente de Castro, Sayonara Pereira da Silva, Nelyane N. M. Santana, Ramon Hypólito Lima, Felipe Porto Fiuza. Aging and Disease, 2025-01-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD), the most common form of dementia, is marked by cognitive decline and amyloid-beta (Aβ) plaque deposition in the brain. Microglia cluster around Aβ plaques shifting to a plaque-associated microglia (PAM) immunophenotype. This study investigates the association between Aβ, microglia and PAM with cognitive performance in 75 older adults, 39 with normal cognition and 36 with AD. Postmortem brain samples containing the middle temporal gyrus (MTG) underwent duplex immunohistochemistry for ionized calcium-binding adaptor molecule 1 (IBA1) and Aβ. A machine learning pipeline quantified parameters of Aβ, microglia and PAM expression. This study evaluated sex- and layer-specific patterns of expression of these parameters and the relationship with global cognitive performance, as measured by the Cognitive Abilities Screening Instrument (CASI) and the Mini-Mental State Examination (MMSE). Additionally, four specific cognitive domains, memory, executive function, language, and visuospatial processing, were evaluated. Aβ and PAM were significantly higher in AD, with no sex- or layer-specific differences. In layers 3 and 4, Aβ plaque size was inversely correlated with MMSE. In all layers, total and activated microglial densities were related to executive function, but in a cognitive status-dependent manner. In layers 5 and 6, higher PAM expression correlated with lower CASI and MMSE scores. PAM expressions in layers 3, 5, and 6 were negatively associated with memory scores. This study characterizes Aβ, microglia, and PAM patterns in the MTG, revealing layer-specific associations between histopathological metrics and cognitive domains. It also highlights PAM as a potential therapeutic target to mitigate cognitive decline in AD.
Key findings
- Aβ and PAM were significantly higher in AD, with no sex- or layer-specific differences.
- PAM expressions in layers 3, 5, and 6 were negatively associated with memory scores.
Why it matters
In postmortem brain tissue from 75 older adults, plaque-associated microglia in certain layers were linked to worse memory scores. This is a study of brain tissue and cognitive scores, not a treatment or prevention strategy.
Study details
- Evidence strengthLow
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging and Disease) |
| Journal's citation record | 1 / 4 | Aging and Disease: journal h-index 107 (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 | 1 / 5 | Rated “low” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.2× 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 | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Felipe Porto Fiuza: h-index 8 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Geneva: institution h-index 1,049 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40423635) |
| Free to read | 2 / 2 | Free to read |
| Total | 35 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Escarião, W. K. M., Silva, G. H., de Castro, H. S. C., da Silva, S. P., Santana, N. N. M., Lima, R. H., et al. (2025). Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease. Aging and Disease. https://doi.org/10.14336/ad.2025.0409
Vancouver
Escarião WKM, Silva GH, de Castro HSC, da Silva SP, Santana NNM, Lima RH, et al. Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease. Aging and Disease. 2025. doi:10.14336/ad.2025.0409. PMID: 40423635.
BibTeX
@article{escariao2025-40423635,
author = {Escarião, Wellydo Kesllowd Marinho and Silva, Guilherme Henrique and de Castro, Hellen Suzane Clemente and da Silva, Sayonara Pereira and Santana, Nelyane N. M. and Lima, Ramon Hypólito and Fiuza, Felipe Porto},
title = {{Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease}},
journal = {Aging and Disease},
year = {2025},
doi = {10.14336/ad.2025.0409},
pmid = {40423635},
url = {https://doi.org/10.14336/ad.2025.0409}
}