Evidence map›Paper›PMID 40361183›Full record

ArticleAlzheimer's research & therapy2025

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, Huiyan Yu, Rong Xiao

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In one paragraph

Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Wenjing FengSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Mengwei JuSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Tao WangSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Shanshan CuiSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Kexin YangSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Zhiting GuoSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Miao LiuSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Jiaxuan TaoSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Huiyan YuSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China.
Rong XiaoSchool of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, China. xiaor22@ccmu.edu.cn.

Funding

National Natural Science Foundation of China 82173501
6 · The paper itself

Abstract

backgroundOxysterols, gut metabolites, and N6-methyladenosine (m6A) are extensively implicated in the pathogenesis of cognitive dysfunction, while their alterations in different stages of mild cognitive impairment (MCI) have not been elucidated. Therefore, this study was conducted to explore the associations of oxysterols, gut metabolites, and m6A methylation profiles in early MCI (EMCI) and late MCI (LMCI) individuals.

methodsLiquid chromatography-mass spectrometry, untargeted metabolomic analysis, and m6A mRNA Epitranscriptomic Microarray were used to detect the characteristics of serum oxysterols (n = 35/group), fecal gut metabolites (n = 30/group), and m6A in whole blood (n = 4/group) respectively. The concentration of serum β-amyloid (Aβ) was detected with ELISA (n = 25/group). The gene expression of amyloid precursor protein (APP) and its key enzyme β-secretase (BACE1) in whole blood were measured by quantitative real-time PCR (n = 25/group).

resultsEMCIs 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.

conclusionsOur 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.

Indexed as

AdenosineCognitive DysfunctionOxysterolsAgedAmyloid beta-PeptidesFemaleHumansMaleAdenosineAmyloid beta-PeptidesN-methyladenosineOxysterolsCognitive assessmentGut metabolitesMild cognitive impairmentN6-methyladenosineOxysterols

Identifiers

PMID40361183
PMCPMC12070570

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.