Deep Profiling of the Aging Proteome Depicts Neuroinflammation, Synaptic Function, and Phosphorylation in an Accelerated Alzheimer's Disease Cell Model.

ABSTRACT: Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by amyloid plaques, tau hyperphosphorylation, and synaptic dysfunction. Most available cellular AD models lack aging features, limiting their ability to recapitulate key pathological mechanisms. Here we applied high-resolution mass spectrometry-based multiplexed proteomics and phosphoproteomics in a discovery setting to characterize an accelerated AD (acAD) model that combines amyloid precursor protein (APP) and presenilin (PSEN) mutations with progerin, an aging-associated Lamin A mutant that accelerates aging. Across four phenotypes (control, progerin, classic AD, and acAD), we identified 8279 proteins, quantified 6081 proteins, and detected phosphorylation dynamics. Relative to the classic model, acAD

SUBMITTER: Gentry E 

PROVIDER: S-EPMC12905760 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature