Altered sphingolipid function in Alzheimer's disease; a gene regulatory network approach

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Sphingolipids (SLs) are crucial for physiological functions and implicated in brain disorders.
• Alzheimer's disease (AD) pathogenesis involves epigenetic dysregulation.
• Understanding the interplay between epigenetics and transcriptomics in AD is vital.

Purpose of the Study:

• To investigate the relationship between epigenetic and transcriptomic alterations in sphingolipid metabolism within the middle temporal gyrus of AD patients.
• To identify key genes and pathways involved in AD pathogenesis related to sphingolipids.

Main Methods:

• Transcriptomic analysis of 252 SL-related genes in 46 AD patients and 32 controls.
• Methylomic analysis to detect hydroxymethylation changes in AD.
• Gene regulatory network analysis to identify candidate genes.

Main Results:

• 103 differentially expressed SL-related genes were identified in AD patients.
• Hydroxymethylation changes were observed in PTGIS, GBA, and ITGB2 genes in AD.
• SELPLG, SPHK1, and CAV1 were identified as candidate genes for therapeutic intervention.

Conclusions:

• Epigenomic and transcriptomic analyses highlight the significance of SL-related genes in AD.
• Identified genes may serve as novel biomarkers for AD.
• This research offers potential therapeutic alternatives beyond traditional pathways for AD treatment.