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Distinct lipid mediator profiles in brain and liver tissues in Alzheimer's disease
Zhou, S.; Borkowski, K.; Liang, N.; Beach, T. G.; Serrano, G.; Kim, K.; Newman, J. W.; Maezawa et al.. medRxiv (preprint), 2026-09-23
Topic: Amyloid, tau and blood-test diagnosis
INTRODUCTIONInflammation plays a central role in Alzheimers Disease (AD), with oxylipins, endocannabinoids, and polyunsaturated fatty acids (PUFAs) acting as potent modulators. Soluble epoxide hydrolase (sEH), an enzyme with proinflammatory products, is upregulated in the AD brain. Emerging evidence suggests that AD-related inflammation may reflect systemic metabolic changes, however, peripheral organs remain understudied. Because the liver has a pivotal role in lipid metabolism and bioactive lipid mediator homeostasis, we hypothesized that inflammatory lipid mediator changes in the AD brain may be reflected in, and potentially shaped by, hepatic lipid metabolism. METHODSPaired postmortem brain and liver tissues from 16 cognitively normal and 63 AD donors with median postmortem intervals (PMI) of 3.08 hours were analyzed for free and esterified forms of oxylipins and endocannabinoids. ANCOVA models evaluated effects of AD diagnosis, sex, and AD-by-sex interactions, adjusting for analytical batch, age, body mass index, and PMI. RESULTSAD-associated differences in lipid mediator profiles were observed in both brain and liver, with a broader pattern of differences in liver. Differences involved CYP/sEH-related metabolites and fatty acid ethanolamides, with several metabolites also showing AD-by-sex interactions. Sex-associated differences were also more pronounced in the liver than the brain. DISCUSSIONThese results suggest AD-associated lipid dysregulation across both central and peripheral tissues. The prominent hepatic alterations highlight the liver as an important site of peripheral lipid mediator dysregulation in AD and suggest that hepatic metabolic changes may contribute to or reflect inflammatory lipid remodeling in the brain.
Key findings
- Emerging evidence suggests that AD-related inflammation may reflect systemic metabolic changes, however, peripheral organs remain understudied.
- DISCUSSIONThese results suggest AD-associated lipid dysregulation across both central and peripheral tissues.
- The prominent hepatic alterations highlight the liver as an important site of peripheral lipid mediator dysregulation in AD and suggest that hepatic metabolic changes may contribute to or reflect inflammatory lipid remodeling in the brain.
Why it matters
This study found differences in inflammatory lipid molecules in both brain and liver tissue from people who had Alzheimer's disease compared to those who did not. The liver showed more widespread changes, suggesting it may play a role in the body-wide inflammation seen in Alzheimer's, but this is tissue analysis and does not test treatments.
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, studied in people and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 20 of the 94 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 (medRxiv (preprint)) |
| 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 | 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Lee‐Way Jin: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Davis: institution h-index 1,257 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 20 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 20 of the 94 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. |
What each of these 20 components measures, and what this score is not →
Read the original
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
Zhou, S., Borkowski, K., Liang, N., Beach, T. G., Serrano, G., Kim, K., et al. (2026). Distinct lipid mediator profiles in brain and liver tissues in Alzheimer's disease. medRxiv (preprint). https://doi.org/10.64898/2026.09.22.26363708
Vancouver
Zhou S, Borkowski K, Liang N, Beach TG, Serrano G, Kim K, et al. Distinct lipid mediator profiles in brain and liver tissues in Alzheimer's disease. medRxiv (preprint). 2026. doi:10.64898/2026.09.22.26363708.
BibTeX
@article{zhou2026-7b25efbc,
author = {Zhou, S. and Borkowski, K. and Liang, N. and Beach, T. G. and Serrano, G. and Kim, K. and Newman, J. W. and Maezawa and others},
title = {{Distinct lipid mediator profiles in brain and liver tissues in Alzheimer's disease}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.22.26363708},
url = {https://doi.org/10.64898/2026.09.22.26363708}
}
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