{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hou X"],"funding":["NINDS NIH HHS"],"pagination":["59"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12669339"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["150(1)"],"pubmed_abstract":["The kinase-ligase pair PINK1-PRKN initiates mitophagy by recognizing and selectively tagging worn-out and dysfunctional mitochondria with phosphorylated ubiquitin (pS65-Ub) to facilitate their elimination via autophagy. In human autopsy brains, the number of pS65-Ub positive cells increases with age but is also associated with Lewy body (LB), neurofibrillary tangles (NFT), and senile plaque (SP) burden. Through a recent genome-wide association study, we identified two genetic modifiers of pS65-Ub levels, APOE4 and ZMIZ1 rs6480922. While LB, NFT, and SP pathologies often coexist in Lewy body dementia (LBD), it is unclear how genetic factors and comorbid neuropathologies interact to impact mitophagy in vulnerable brain regions. We therefore measured levels of the age and disease marker pS65-"],"journal":["Acta neuropathologica"],"pubmed_title":["Genetic factors and comorbid pathologies interact to drive regional mitophagy alterations in Lewy body dementia."],"pmcid":["PMC12669339"],"funding_grant_id":["U54NS110435"],"pubmed_authors":["Fiesel FC","Dickson DW","Richardson T","Heckman MG","Springer W","Koga S","Ross OA","White LJ","Hou X"],"additional_accession":[]},"is_claimable":false,"name":"Genetic factors and comorbid pathologies interact to drive regional mitophagy alterations in Lewy body dementia.","description":"The kinase-ligase pair PINK1-PRKN initiates mitophagy by recognizing and selectively tagging worn-out and dysfunctional mitochondria with phosphorylated ubiquitin (pS65-Ub) to facilitate their elimination via autophagy. In human autopsy brains, the number of pS65-Ub positive cells increases with age but is also associated with Lewy body (LB), neurofibrillary tangles (NFT), and senile plaque (SP) burden. Through a recent genome-wide association study, we identified two genetic modifiers of pS65-Ub levels, APOE4 and ZMIZ1 rs6480922. While LB, NFT, and SP pathologies often coexist in Lewy body dementia (LBD), it is unclear how genetic factors and comorbid neuropathologies interact to impact mitophagy in vulnerable brain regions. We therefore measured levels of the age and disease marker pS65-","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-05T21:50:26.314Z","creation":"2026-05-22T03:15:21.977Z"},"accession":"S-EPMC12669339","cross_references":{"pubmed":["41326741"],"doi":["10.1007/s00401-025-02964-6"]}}