Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine DOI Creative Commons
Wenjing Feng, Mengwei Ju, Tao Wang

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: May 13, 2025

Oxysterols, gut metabolites, and N6-methyladenosine (m6A) are extensively implicated in the pathogenesis of cognitive dysfunction, while their alterations different stages mild impairment (MCI) have not been elucidated. Therefore, this study was conducted to explore associations oxysterols, m6A methylation profiles early MCI (EMCI) late (LMCI) individuals. Liquid chromatography-mass spectrometry, untargeted metabolomic analysis, mRNA Epitranscriptomic Microarray were used detect characteristics serum oxysterols (n = 35/group), fecal metabolites 30/group), whole blood 4/group) respectively. The concentration β-amyloid (Aβ) detected with ELISA 25/group). gene expression amyloid precursor protein (APP) its key enzyme β-secretase (BACE1) measured by quantitative real-time PCR EMCIs LMCIs, especially exhibited poorer performance almost all global multidimensional tests. Serum 27-hydroxycholesterol (27-OHC) 24S-hydroxycholesterol (24S-OHC) elevated EMCI LMCI groups. Changes occurred mainly group, which several including Procyanidin dimer B7 Phorbol myristate, significantly decreased. landscape LMCIs obviously differed from Controls. Hypomethylated mRNAs accounted for majority accompanied downregulated mRNAs, consistent writer methyltransferase-like 4 (METTL4). 27-OHC 24S-OHC combined various distinguished between subgroups healthy controls (EMCI/Control: AUC 0.877; LMCI/Control: 0.952). Heatmap revealed correlation myristate differentially m6A-methylated mRNAs. Differentially expressed methylated commonly enriched 34 KEGG metabolic pathways, cholesterol metabolism neurodegenerative disease-related pathways. Our explored altered MCI. potential function aberrant driving progression warrants further mechanistic investigation.

Language: Английский

Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine DOI Creative Commons
Wenjing Feng, Mengwei Ju, Tao Wang

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: May 13, 2025

Oxysterols, gut metabolites, and N6-methyladenosine (m6A) are extensively implicated in the pathogenesis of cognitive dysfunction, while their alterations different stages mild impairment (MCI) have not been elucidated. Therefore, this study was conducted to explore associations oxysterols, m6A methylation profiles early MCI (EMCI) late (LMCI) individuals. Liquid chromatography-mass spectrometry, untargeted metabolomic analysis, mRNA Epitranscriptomic Microarray were used detect characteristics serum oxysterols (n = 35/group), fecal metabolites 30/group), whole blood 4/group) respectively. The concentration β-amyloid (Aβ) detected with ELISA 25/group). gene expression amyloid precursor protein (APP) its key enzyme β-secretase (BACE1) measured by quantitative real-time PCR EMCIs LMCIs, especially exhibited poorer performance almost all global multidimensional tests. Serum 27-hydroxycholesterol (27-OHC) 24S-hydroxycholesterol (24S-OHC) elevated EMCI LMCI groups. Changes occurred mainly group, which several including Procyanidin dimer B7 Phorbol myristate, significantly decreased. landscape LMCIs obviously differed from Controls. Hypomethylated mRNAs accounted for majority accompanied downregulated mRNAs, consistent writer methyltransferase-like 4 (METTL4). 27-OHC 24S-OHC combined various distinguished between subgroups healthy controls (EMCI/Control: AUC 0.877; LMCI/Control: 0.952). Heatmap revealed correlation myristate differentially m6A-methylated mRNAs. Differentially expressed methylated commonly enriched 34 KEGG metabolic pathways, cholesterol metabolism neurodegenerative disease-related pathways. Our explored altered MCI. potential function aberrant driving progression warrants further mechanistic investigation.

Language: Английский

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