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Hepatic and Brain Spatial Gene Expression Changes in Intragastric Alcohol Fed APP/PS1 Alzheimer's Disease Mouse Model
Duche A, Chandnra DV, Han D, Sumbria RK, Rahman M.. Research Square, 2026-08-24
Topic: Genetics and APOE
Background Alcohol use is increasingly recognized as a significant modifier of Alzheimer's disease (AD) risk and progression. Results Following alcohol exposure, the most prominent transcriptional changes in the liver occurred in the perivenous zone, followed by the periportal zone. These findings highlight Aβ pathology-dependent and region-selective tissue vulnerability to alcohol in the brain and liver during AD. This revealed coordinated molecular perturbations, including shared downregulation of S100a8 and Tmem267 , as well as opposing regulation of Lrp1 , Osgin1 , and Cpsf7 between the plaque-bearing hippocampus and perivenous liver ROIs, respectively. Conclusion These findings implicate significant liver–brain crosstalk through which chronic alcohol exposure may modulate AD-relevant pathology and reinforce the growing recognition of the liver as a critical organ in AD pathogenesis. Furthermore, these results reveal key alcohol-driven hepatic and brain gene perturbations and dysregulated pathways relevant to AD along with actionable therapeutic targets for future investigation.
Key findings
- Background Alcohol use is increasingly recognized as a significant modifier of Alzheimer's disease (AD) risk and progression.
- Results Following alcohol exposure, the most prominent transcriptional changes in the liver occurred in the perivenous zone, followed by the periportal zone.
- These findings highlight Aβ pathology-dependent and region-selective tissue vulnerability to alcohol in the brain and liver during AD.
- This revealed coordinated molecular perturbations, including shared downregulation of S100a8 and Tmem267 , as well as opposing regulation of Lrp1 , Osgin1 , and Cpsf7 between the plaque-bearing hippocampus and perivenous liver ROIs, respectively.
- Conclusion These findings implicate significant liver–brain crosstalk through which chronic alcohol exposure may modulate AD-relevant pathology and reinforce the growing recognition of the liver as a critical organ in AD pathogenesis.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | Laboratory or animal study (title names “app/ps1”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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APA 7th
Duche, A., Chandnra, D. V., Han, D., Sumbria, R. K., & Rahman, M. (2026). Hepatic and Brain Spatial Gene Expression Changes in Intragastric Alcohol Fed APP/PS1 Alzheimer's Disease Mouse Model. Research Square. https://doi.org/10.21203/rs.3.rs-10760512/v1
Vancouver
Duche A, Chandnra DV, Han D, Sumbria RK, Rahman M. Hepatic and Brain Spatial Gene Expression Changes in Intragastric Alcohol Fed APP/PS1 Alzheimer's Disease Mouse Model. Research Square. 2026. doi:10.21203/rs.3.rs-10760512/v1.
BibTeX
@article{duche2026-0146b3bc,
author = {Duche, A. and Chandnra, D. V. and Han, D. and Sumbria, R. K. and Rahman, M.},
title = {{Hepatic and Brain Spatial Gene Expression Changes in Intragastric Alcohol Fed APP/PS1 Alzheimer's Disease Mouse Model}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10760512/v1},
url = {https://doi.org/10.21203/rs.3.rs-10760512/v1}
}