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Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine
Wenjing Feng, Mengwei Ju, Tao Wang, Shanshan Cui, Kexin Yang, Zhiting Guo, Miao Liu, Jiaxuan Tao et al.. Alzheimer s Research & Therapy, 2025-05-13
Topic: Brain proteins, microglia and lab models
EMCIs and LMCIs, especially LMCIs, exhibited poorer performance in almost all global and multidimensional cognitive tests. Serum 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) were elevated in EMCI and LMCI groups. Changes in gut metabolites occurred mainly in the EMCI group, in which several gut metabolites, including Procyanidin dimer B7 and Phorbol myristate, were significantly decreased. The m6A methylation landscape of EMCIs and LMCIs obviously differed from Controls. Hypomethylated mRNAs accounted for the majority and were mainly accompanied by downregulated mRNAs, which was consistent with the downregulated expression of the m6A writer methyltransferase-like 4 (METTL4). 27-OHC and 24S-OHC combined with various gut metabolites significantly distinguished between MCI subgroups from healthy controls (EMCI/Control: AUC = 0.877; LMCI/Control: AUC = 0.952). Heatmap revealed the correlation between Phorbol myristate and differentially m6A-methylated mRNAs. Differentially expressed gut metabolites and methylated mRNAs were commonly enriched in 34 KEGG metabolic pathways, including cholesterol metabolism and neurodegenerative disease-related pathways. Our study explored the altered oxysterols, gut metabolites, and m6A methylation and their associations in different stages of MCI. The potential function of aberrant gut metabolites in oxysterols and m6A methylation driving MCI progression warrants further mechanistic investigation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Feng, W., Ju, M., Wang, T., Cui, S., Yang, K., Guo, Z., et al. (2025). Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine. Alzheimer s Research & Therapy. https://doi.org/10.1186/s13195-025-01743-5
Vancouver
Feng W, Ju M, Wang T, Cui S, Yang K, Guo Z, et al. Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine. Alzheimer s Research & Therapy. 2025. doi:10.1186/s13195-025-01743-5. PMID: 40361183.
BibTeX
@article{feng2025-40361183,
author = {Feng, Wenjing and Ju, Mengwei and Wang, Tao and Cui, Shanshan and Yang, Kexin and Guo, Zhiting and Liu, Miao and Tao, Jiaxuan and others},
title = {{Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine}},
journal = {Alzheimer s Research \& Therapy},
year = {2025},
doi = {10.1186/s13195-025-01743-5},
pmid = {40361183},
url = {https://doi.org/10.1186/s13195-025-01743-5}
}
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
- EMCIs and LMCIs, especially LMCIs, exhibited poorer performance in almost all global and multidimensional cognitive tests.
- Serum 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) were elevated in EMCI and LMCI groups.
- Changes in gut metabolites occurred mainly in the EMCI group, in which several gut metabolites, including Procyanidin dimer B7 and Phorbol myristate, were significantly decreased.
- The m6A methylation landscape of EMCIs and LMCIs obviously differed from Controls.
- Hypomethylated mRNAs accounted for the majority and were mainly accompanied by downregulated mRNAs, which was consistent with the downregulated expression of the m6A writer methyltransferase-like 4 (METTL4). 27-OHC and 24S-OHC combined with various gut metabolites significantly distinguished between MCI subgroups from healthy controls (EMCI/Control: AUC = 0.877; LMCI/Control: AUC = 0.952).
Why it matters
This study found altered oxysterols, gut metabolites, and m6A methylation in different stages of mild cognitive impairment, with some combinations distinguishing MCI subgroups from healthy controls. It is an exploratory analysis of associations and does not show that targeting these markers treats, cures, or prevents Alzheimer's disease.
Study details
- Participants35
- Effect sizeAUC = 0.877; AUC = 0.952
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design 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 (Alzheimer s Research & Therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (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 | 1 / 4 | 35 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.9× 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 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Rong Xiao holds only 8 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40361183) |
| 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: 10.1186/s13195-025-01743-5
- PubMed: 40361183
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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