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Ethanol consumption aggravates amyloid pathology and neuroinflammation in Alzheimer’s disease associated with inflammasome activation and ASC speck propagation
Veronika Brezáni, Radhika Joshi, Martí Ortega‐Ribera, Prashanth Thevkar Nagesh, Veronika Brezáni, Adam Zivny, Evelyn A. Kurt‐Jones, Douglas Taylor Golenbock et al.. Journal of Neuroinflammation, 2025-07-15
Topic: Amyloid, tau and blood-test diagnosis
In this study, we show that repeated ethanol binges aggravate the amyloid pathology and plaque burden in the hippocampus of APP/PS1 mice. Furthermore, we demonstrate the additive effect of ethanol administration on NLRP3 inflammasome activation, IL-1β release, and ASC aggregation in the brains of APP/PS1 mice and primary glia cultures. Our study also reveals a strong astrocyte activation by ethanol in the hippocampus of APP/PS1 mice as demonstrated by significantly increased GFAP and ALDH1L1 protein levels. Further in vitro analysis revealed that ethanol potentiates the effect of amyloid β to increase the NLRP3 inflammasome activation in both primary astrocytes and microglia. Lastly, we demonstrate that glia-produced ASC specks induce IL-1β in microglia and astrocytes and induce ROS in SH-SY5Y neurons, contributing to sustained neuroinflammation in AD. Collectively, our results demonstrate that ethanol consumption exacerbates features of AD pathology associated with amplified neuroinflammation and NLRP3/ASC inflammasome activation, which may play an important role in the disease progression and severity.
Key findings
- In this study, we show that repeated ethanol binges aggravate the amyloid pathology and plaque burden in the hippocampus of APP/PS1 mice.
- Furthermore, we demonstrate the additive effect of ethanol administration on NLRP3 inflammasome activation, IL-1β release, and ASC aggregation in the brains of APP/PS1 mice and primary glia cultures.
- Our study also reveals a strong astrocyte activation by ethanol in the hippocampus of APP/PS1 mice as demonstrated by significantly increased GFAP and ALDH1L1 protein levels.
- Further in vitro analysis revealed that ethanol potentiates the effect of amyloid β to increase the NLRP3 inflammasome activation in both primary astrocytes and microglia.
- Lastly, we demonstrate that glia-produced ASC specks induce IL-1β in microglia and astrocytes and induce ROS in SH-SY5Y neurons, contributing to sustained neuroinflammation in AD.
Why it matters
In mice with Alzheimer's-like pathology, repeated heavy drinking increased amyloid plaques and brain inflammation. This suggests that heavy alcohol use may worsen Alzheimer's-related brain changes, though the findings come from animal models.
Study details
- Evidence strengthLow
How this study scored 45/100
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 (Journal of Neuroinflammation) |
| Journal's citation record | 2 / 4 | Journal of Neuroinflammation: journal h-index 216 (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 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.9× 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 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Gyöngyi Szabó: h-index 106 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40665351) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s12974-025-03501-8
- PubMed: 40665351
- Original source →
- Free full text: Journal of Neuroinflammation →
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
Brezáni, V., Joshi, R., Ortega‐Ribera, M., Nagesh, P. T., Zivny, A., Kurt‐Jones, E. A., et al. (2025). Ethanol consumption aggravates amyloid pathology and neuroinflammation in Alzheimer’s disease associated with inflammasome activation and ASC speck propagation. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-025-03501-8
Vancouver
Brezáni V, Joshi R, Ortega‐Ribera M, Nagesh PT, Zivny A, Kurt‐Jones EA, et al. Ethanol consumption aggravates amyloid pathology and neuroinflammation in Alzheimer’s disease associated with inflammasome activation and ASC speck propagation. Journal of Neuroinflammation. 2025. doi:10.1186/s12974-025-03501-8. PMID: 40665351.
BibTeX
@article{brezani2025-40665351,
author = {Brezáni, Veronika and Joshi, Radhika and Ortega‐Ribera, Martí and Nagesh, Prashanth Thevkar and Zivny, Adam and Kurt‐Jones, Evelyn A. and Golenbock, Douglas Taylor and others},
title = {{Ethanol consumption aggravates amyloid pathology and neuroinflammation in Alzheimer’s disease associated with inflammasome activation and ASC speck propagation}},
journal = {Journal of Neuroinflammation},
year = {2025},
doi = {10.1186/s12974-025-03501-8},
pmid = {40665351},
url = {https://doi.org/10.1186/s12974-025-03501-8}
}
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