Human and mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome.

ABSTRACT: Murine models of Alzheimer's disease (AD) are crucial for elucidating disease mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse models of amyloidosis. We identified shared pathways by integrating with human metadata and prioritized components by multi-omics analysis. Collectively, two commonly used models (5xFAD and APP-KI) replicate 30% of the human protein alterations; additional genetic incorporation of tau and splicing pathologies increases this similarity to 42%. We dissected the proteome-transcriptome inconsistency in AD and 5xFAD mouse brains, revealing that inconsistent proteins are enriched within amyloid plaque microenvironment (amyloidome). Our

SUBMITTER: Yarbro JM 

PROVIDER: S-EPMC11814087 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature