biostudies-literatureUnknown17Pahal S<h4>Background</h4>Mitochondrial dysfunction and protein aggregation are central features of brain aging and Alzheimer's disease (AD). To define how AD seed proteins modulate these processes, we applied quantitative proteomics to sarkosyl-insoluble aggregates from <i>C. elegans</i> models of normal aging and from worms expressing human Aβ or Tau transgenes.<h4>Results</h4>Normal aging produced a late-onset accrual of mitochondrial proteins within aggregates, implicating impaired energy metabolism and proteostasis collapse. Aβ expression caused a striking expansion and included glycolytic enzymes, tricarboxylic acid cycle components, ribosomal proteins, and trafficking factors, consistent with broad proteostatic and bioenergetic stress, largely overlapping with aging-associated species, yetFrontiers in aging neuroscience1713391https://www.ebi.ac.uk/biostudies/studies/S-EPMC12835372biostudies-literatureThe aggregate proteome of <i>Caenorhabditis elegans</i> mitochondria implicates shared mechanisms of aging and Alzheimer's disease.PMC12835372Ayyadevara SShmookler Reis RJGriffin STPahal SGanne ABalasubramaniam MfalseThe aggregate proteome of <i>Caenorhabditis elegans</i> mitochondria implicates shared mechanisms of aging and Alzheimer's disease.<h4>Background</h4>Mitochondrial dysfunction and protein aggregation are central features of brain aging and Alzheimer's disease (AD). To define how AD seed proteins modulate these processes, we applied quantitative proteomics to sarkosyl-insoluble aggregates from <i>C. elegans</i> models of normal aging and from worms expressing human Aβ or Tau transgenes.<h4>Results</h4>Normal aging produced a late-onset accrual of mitochondrial proteins within aggregates, implicating impaired energy metabolism and proteostasis collapse. Aβ expression caused a striking expansion and included glycolytic enzymes, tricarboxylic acid cycle components, ribosomal proteins, and trafficking factors, consistent with broad proteostatic and bioenergetic stress, largely overlapping with aging-associated species, yet2025-01-01T00:00:00Z20252026-06-16T03:20:01.665Z2026-06-16T03:10:00.896ZS-EPMC128353724160750510.3389/fnagi.2025.1713391