Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer’s disease DOI Creative Commons

Tingting Ruan,

Yunxiang Ling,

Can Wu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background Abnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for metabolism. However, the epigenetic modifications lysosome and regulating genes remain unclear in AD patients. Objective Explore role abnormal modifications, especially methylation metabolism-related AD. Methods Methylation beadchip MALDI-TOF mass spectrometry were used to detect genome-wide DNA levels validate key gene methylation, respectively. Clinical data collected from all participants. Associations between clinical biochemical characteristics altered patients analyzed, risk factor model was established. Results 41 differentially methylated positions (DMPs) corresponding 33 patients, with 18 hypermethylated 23 hypomethylated positions. Significant alterations observed ( CTNNB1, DGKQ, SLC27A1 ) lysosomal transmembrane TMEM175 ). analysis revealed that TP, ALB, IB, ADA, ALP, HCY, GLU, TC, BUN, HDL-C, LDL-C, APOA1 significantly higher whereas A/G DB lower. hypermethylation further verified found correlate APOA1, HCY. The AUC model, integrated markers reached 0.9519 p < 0.0001). Conclusions regulation dyshomeostasis high-risk factors processes pathogenesis.

Language: Английский

Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer’s disease DOI Creative Commons

Tingting Ruan,

Yunxiang Ling,

Can Wu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background Abnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for metabolism. However, the epigenetic modifications lysosome and regulating genes remain unclear in AD patients. Objective Explore role abnormal modifications, especially methylation metabolism-related AD. Methods Methylation beadchip MALDI-TOF mass spectrometry were used to detect genome-wide DNA levels validate key gene methylation, respectively. Clinical data collected from all participants. Associations between clinical biochemical characteristics altered patients analyzed, risk factor model was established. Results 41 differentially methylated positions (DMPs) corresponding 33 patients, with 18 hypermethylated 23 hypomethylated positions. Significant alterations observed ( CTNNB1, DGKQ, SLC27A1 ) lysosomal transmembrane TMEM175 ). analysis revealed that TP, ALB, IB, ADA, ALP, HCY, GLU, TC, BUN, HDL-C, LDL-C, APOA1 significantly higher whereas A/G DB lower. hypermethylation further verified found correlate APOA1, HCY. The AUC model, integrated markers reached 0.9519 p < 0.0001). Conclusions regulation dyshomeostasis high-risk factors processes pathogenesis.

Language: Английский

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