Epigenetic and transcriptomic alterations precede amyloidosis in the Alzheimer's disease App^NL-G-F knock-in mouse model.

ABSTRACT: Understanding Alzheimer's disease (AD) from its earliest stages is essential for uncovering initial mechanisms of pathology and developing interventions. Here, we use the humanized App^NL-G-F mouse model, which develops early amyloid pathology along a predictable timeline, to characterize epigenetic changes in the brain and blood at early pre-symptomatic, as well as later, stages of disease progression. We identified alterations in chromatin accessibility, gene expression, and DNA methylation before and after amyloidosis, in the absence of advanced age. Despite broadly stable hippocampal cell composition, App^NL-G-F mice exhibit major gene expression differences preceding amyloid plaque deposition, particularly in pathways related to mitochondrial function and protein b

SUBMITTER: Okhovat M 

PROVIDER: S-EPMC12748836 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature