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Microglial histone H3K18 crotonylation promotes STAT1 expression and induces cognitive deficit in Alzheimer disease
Ying Weng, Ting He, Mengzhu Li, Qiuzhi Zhou, Jiazhao Xie, Linyu Wei, Xin Wang, Jian-Zhi Wang et al.. Frontiers in Immunology, 2026-01-27
Topic: Brain proteins, microglia and lab models
Hippocampal pan-histone H3 crotonylation (H3Kcr) and H3K18cr were significantly upregulated in both 5xFAD and Aβ42-injected mice compared to controls. ICV injection of crotonic acid markedly elevated hippocampal H3Kcr and H3K18cr levels and induced significant cognitive deficits, shown by impaired novel object recognition and fear conditioning performance. Crotonic acid treatment resulted in synaptic dysfunction, including reduced synaptic markers (SYN1, SYT, GluA2, GluN2B) and decreased CA1 dendritic spine density. Crotonic acid also induced microgliosis with elevated Iba1 expression. H3K18cr was specifically upregulated in microglia, with no significant changes observed in neurons or astrocytes. Transcriptomic analysis identified 478 differentially expressed genes enriched predominantly in immune-related pathways, with STAT1 highlighted as a key upstream transcription factor. In BV2 cells, crotonic acid significantly increased total and phosphorylated STAT1 (Tyr701) levels via a JAK1-independent mechanism. Treatment with fludarabine effectively suppressed STAT1 expression and attenuated the production of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β. This study provides the first evidence that elevated microglial H3K18cr contributes to AD-related cognitive impairment by promoting STAT1 expression and subsequent neuroinflammation. These findings identify microglial histone crotonylation as a novel epigenetic mechanism in AD pathogenesis and suggest that targeting the H3K18cr-STAT1 axis may represent a potential therapeutic strategy for AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Weng, Y., He, T., Li, M., Zhou, Q., Xie, J., Wei, L., et al. (2026). Microglial histone H3K18 crotonylation promotes STAT1 expression and induces cognitive deficit in Alzheimer disease. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2026.1744375
Vancouver
Weng Y, He T, Li M, Zhou Q, Xie J, Wei L, et al. Microglial histone H3K18 crotonylation promotes STAT1 expression and induces cognitive deficit in Alzheimer disease. Frontiers in Immunology. 2026. doi:10.3389/fimmu.2026.1744375. PMID: 41676156.
BibTeX
@article{weng2026-41676156,
author = {Weng, Ying and He, Ting and Li, Mengzhu and Zhou, Qiuzhi and Xie, Jiazhao and Wei, Linyu and Wang, Xin and Wang, Jian-Zhi and others},
title = {{Microglial histone H3K18 crotonylation promotes STAT1 expression and induces cognitive deficit in Alzheimer disease}},
journal = {Frontiers in Immunology},
year = {2026},
doi = {10.3389/fimmu.2026.1744375},
pmid = {41676156},
url = {https://doi.org/10.3389/fimmu.2026.1744375}
}
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.
Key findings
- Hippocampal pan-histone H3 crotonylation (H3Kcr) and H3K18cr were significantly upregulated in both 5xFAD and Aβ42-injected mice compared to controls.
- ICV injection of crotonic acid markedly elevated hippocampal H3Kcr and H3K18cr levels and induced significant cognitive deficits, shown by impaired novel object recognition and fear conditioning performance.
- Crotonic acid treatment resulted in synaptic dysfunction, including reduced synaptic markers (SYN1, SYT, GluA2, GluN2B) and decreased CA1 dendritic spine density.
- Crotonic acid also induced microgliosis with elevated Iba1 expression.
- H3K18cr was specifically upregulated in microglia, with no significant changes observed in neurons or astrocytes.
Why it matters
In mice and cells, elevated microglial H3K18cr promoted STAT1 expression and neuroinflammation, and fludarabine suppressed STAT1 and reduced pro-inflammatory cytokines. This is early animal and cell research, so it does not show a treatment or prevention for Alzheimer's disease in humans.
Study details
- Evidence strengthLow
How this study scored 41/100
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. We have no data on senior author's track record, so that was left out: it earned 39 of the 96 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Immunology) |
| Journal's citation record | 3 / 4 | Frontiers in Immunology: journal h-index 352 (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 | 5 / 5 | 2026 — within 1 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 | 2.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 16.6× 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 | — / 4 | OpenAlex's profile for last-listed author Shihong Li holds only 4 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | Huazhong University of Science and Technology: institution h-index 934 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41676156) |
| Free to read | 2 / 2 | Free to read |
| Points | 39 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 39 of the 96 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fimmu.2026.1744375
- PubMed: 41676156
- Original source →
- Free full text: Frontiers in Immunology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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