Higher Intron Retention Levels in Female Alzheimer's Brains May Be Linked to Disease Prevalence.

ABSTRACT: Multimodal study of Alzheimer's disease (AD) dorsolateral prefrontal cortex (DLPFC) showed AD-related aberrant intron retention (IR) and proteomic changes not observed at the RNA level. However, the role of sex and how IR may impact the proteome are unclear. Analysis of DLPFC transcriptome showed a clear sex-biased pattern where female AD had 1645 elevated IR events compared to 80 in male AD DLPFC. Increased IR is correlated with lower mRNA levels, suggestive of nonsense-mediated mRNA decay. Two hundred thirty-three mRNAs with elevated IR in females were curated AD genes enriched for ubiquitin-like protein ligase and Tau protein binding. Increased IR genes in combined sex and female AD cohorts showed significant changes in their protein expression patterns with 11%-24% of them differential

SUBMITTER: Choo CT 

PROVIDER: S-EPMC11822637 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature