Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance.

ABSTRACT: Alzheimer's disease (AD) is a relentlessly progressive, fatal neurodegenerative disorder associated with widespread aberrant proteomic changes. The full extent of protein dysfunctions in AD and their impact on cellular physiology remains unknown. Here, we used plexDIA, an approach that parallelizes the acquisition of samples and peptides, to characterize proteomic changes in AD. Using human dorsolateral prefrontal cortex tissue, we identified 281 differentially abundant proteins in AD. By systematically analyzing cellular compartment-specific shifts in protein abundance, we identified an AD-specific decrease in levels of the 20S proteasome, the catalytic core of the cell's primary protein degradation pathway. This alteration was accompanied by widespread decreases in proteasome subunit sto

SUBMITTER: Collins M 

PROVIDER: S-EPMC12154775 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature