Disruption of hnRNP A2-mediated RNA dynamics by amyloid-β drives MBP increase in Alzheimer's disease.

ABSTRACT: Oligodendrocyte dysfunction, myelin degeneration, and white matter changes are critical events in the cognitive decline of Alzheimer's disease (AD). Amyloid-β peptide (Aβ), a hallmark of AD, disrupts oligodendrocyte and myelin homeostasis, through mechanisms that remain poorly understood. Here, transcriptomic profiling of Aβ-exposed oligodendrocytes revealed widespread gene expression changes, particularly in RNA-related processes. Among these, hnRNP A2, a key regulator of RNA transport and myelin protein regulation, was aberrantly upregulated in hippocampal oligodendrocytess from AD patients with high Aβ levels, from AD mouse models, and in Aβ-treated oligodendrocytes. RNA-immunoprecipitation sequencing of the hnRNP A2 interactome revealed Aβ-induced changes in mRNA interactions, particul

SUBMITTER: Gaminde-Blasco A 

PROVIDER: S-EPMC12317959 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature