{"doi":"10.1101/2022.01.18.22269350","title":"Single-nuclei paired multiomic analysis of young, aged, and Parkinson’s disease human midbrain reveals age- and disease-associated glial changes and their contribution to Parkinson’s disease","abstract":"Abstract Age is the primary risk factor for Parkinson’s disease (PD), but how aging changes the expression and regulatory landscape of the brain remains unclear. Here, we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD post-mortem midbrain samples. Combined multiomic analysis along a pseudopathogenesis trajectory reveals all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We present evidence for a novel disease-associated oligodendrocyte subtype and identify genes lost over the aging and disease process, including CARNS1, that may predispose healthy cells to develop a disease-associated phenotype. Peak-gene association analysis from paired data identifies 89 PD-associated SNP loci, including five in MAPT, that show differential association with gene expression in disease-associated oligodendrocytes. Our study suggests a previously undescribed role for oligodendrocytes in aging and PD pathogenesis.","journal":"medRxiv","year":2022,"id":297851,"datarank":0.3997428849297943,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0878266536778189,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0878266536778189,"corpus_percentile":54.212114179624045,"corpus_rank":5920,"citation_count":7,"citer_count":6,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8147,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":686611,"name":"Min Kyung Song","orcid":"0000-0002-1779-5992","position":1,"is_corresponding":false},{"id":237105,"name":"Yoshiaki Tanaka","orcid":"0000-0002-2078-9374","position":2,"is_corresponding":false},{"id":573675,"name":"Yoon‐Seong Kim","orcid":"0000-0001-6246-5477","position":3,"is_corresponding":false},{"id":887752,"name":"Levi Adams","orcid":null,"position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:31:31.270564Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}