{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:54:31Z","timestamp":1788245671026,"version":"build-2803163510"},"reference-count":0,"publisher":"Aging and Disease","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["aging dis"],"abstract":"<jats:p>Phosphorylated ubiquitin (pS65-Ub) is generated by the kinase-ligase pair PINK1-Parkin to selectively label damaged mitochondria for degradation via the autophagy-lysosome system (mitophagy). Consistent with increasing mitochondrial and lysosomal dysfunctions, pS65-Ub accumulates with aging in human autopsy brain and in mice. pS65-Ub levels are strongly and independently elevated in brains from subjects with Alzheimer\u2019s or Parkinson\u2019s disease compared to age-matched, neurologically normal controls. Furthermore, pS65-Ub levels have been used to identify disease risk and potential resilience factors in cells and in human brain. However, it remains unknown whether pS65-Ub measured in biofluids may also be suitable as a clinical biomarker. Here, we used a validated sandwich ELISA based on the Mesoscale discovery platform to assess pS65-Ub levels in over 1500 plasma samples from different cohorts across a spectrum of mild cognitive impairment, Alzheimer\u2019s disease, or Parkinson\u2019s disease. We further analyzed almost 150 CSF samples from two independent case-control series with Parkinson\u2019s disease to determine whether pS65-Ub levels are associated with disease status and other clinical parameters. While pS65-Ub levels are significantly changed with disease compared to controls in certain samples, current measurements in plasma are not sufficiently discriminatory to serve as a robust diagnostic marker. However, in CSF, pS65-Ub levels were decreased in patients with Parkinson\u2019s disease compared to controls, and there was better discrimination between these groups. Our data indicate that pS65-Ub shows promise as a biomarker in CSF but will require further replication in larger cohorts and possibly in combination with additional other measures.<\/jats:p>","DOI":"10.14336\/ad.2025.1220","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T17:18:26Z","timestamp":1764955106000},"source":"Crossref","is-referenced-by-count":5,"title":["Phosphorylated Ubiquitin as a Clinical Biomarker for Mitochondrial Damage in Neurodegenerative Diseases"],"prefix":"10.14336","member":"5462","published-online":{"date-parts":[[2025]]},"container-title":["aging and disease"],"original-title":[],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T17:18:27Z","timestamp":1764955107000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2025.1220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14336\/ad.2025.1220","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]}}}