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Proliferating Microglia Exhibit Unique Transcriptional and Functional Alterations in Alzheimer’s Disease
Nàdia Villacampa, Heela Sarlus, Paula Martorell, Khushbu Bhalla, Sergio Castro‐Gomez, Ana Maria Menezes Vieira-Saecker, Ilya Slutzkin, Kristian Händler et al.. ASN NEURO, 2025-05-19
Topic: Amyloid, tau and blood-test diagnosis
Proliferation of microglia represents a physiological process, which is accelerated in several neurodegenerative disorders including Alzheimer disease (AD). The effect of such neurodegeneration-associated microglial proliferation on function and disease progression remains unclear. Here, we show that proliferation results in profound alterations of cellular function by providing evidence that newly proliferated microglia show impaired beta-amyloid clearance in vivo. Through sorting of proliferating microglia of APP/PS1 mice and subsequent transcriptome analysis, we define unique proliferation-associated transcriptomic signatures that change with age and beta-amyloid accumulation and are characterized by enrichment of immune system-related pathways. Of note, we identify the DEAD-Box Helicase 3 X-Linked (DDX3X) as a key molecule to modulate microglia activation and cytokine secretion and it is expressed in the AD brain. Together, these results argue for a novel concept by which phenotypic and functional microglial changes occur longitudinally as a response to accelerated proliferation in a neurodegenerative environment.
Key findings
- Here, we show that proliferation results in profound alterations of cellular function by providing evidence that newly proliferated microglia show impaired beta-amyloid clearance in vivo.
- Together, these results argue for a novel concept by which phenotypic and functional microglial changes occur longitudinally as a response to accelerated proliferation in a neurodegenerative environment.
Why it matters
In mice with Alzheimer's-like pathology, newly divided microglia cleared beta-amyloid less effectively, and a molecule called DDX3X was identified as influencing microglial activation. This is early animal and laboratory work that points to a possible role of microglial proliferation in disease progression.
Study details
- Evidence strengthLow
How this study scored 39/100
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 (ASN NEURO) |
| Journal's citation record | 0 / 4 | ASN NEURO: journal h-index 71 (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 | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.4× 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 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Michael Thomas Heneka: h-index 113 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Weizmann Institute of Science: institution h-index 1,080 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40387894) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Villacampa, N., Sarlus, H., Martorell, P., Bhalla, K., Castro‐Gomez, S., Vieira-Saecker, A. M. M., et al. (2025). Proliferating Microglia Exhibit Unique Transcriptional and Functional Alterations in Alzheimer’s Disease. ASN NEURO. https://doi.org/10.1080/17590914.2025.2506406
Vancouver
Villacampa N, Sarlus H, Martorell P, Bhalla K, Castro‐Gomez S, Vieira-Saecker AMM, et al. Proliferating Microglia Exhibit Unique Transcriptional and Functional Alterations in Alzheimer’s Disease. ASN NEURO. 2025. doi:10.1080/17590914.2025.2506406. PMID: 40387894.
BibTeX
@article{villacampa2025-40387894,
author = {Villacampa, Nàdia and Sarlus, Heela and Martorell, Paula and Bhalla, Khushbu and Castro‐Gomez, Sergio and Vieira-Saecker, Ana Maria Menezes and Slutzkin, Ilya and Händler, Kristian and others},
title = {{Proliferating Microglia Exhibit Unique Transcriptional and Functional Alterations in Alzheimer’s Disease}},
journal = {ASN NEURO},
year = {2025},
doi = {10.1080/17590914.2025.2506406},
pmid = {40387894},
url = {https://doi.org/10.1080/17590914.2025.2506406}
}
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