{"doi":"10.1093/jnen/nlaf137","title":"A novel hierarchical framework elucidating regional differences in α-synuclein and tau co-pathology in military veterans with parkinsonism","abstract":"Neuropathologic features diagnostic of parkinsonian disorders infrequently occur in isolation; hyperphosphorylated tau (p-tau) and amyloid plaques are often observed in combination with α-synuclein deposition. Co-pathologies in neurodegenerative diseases are now recognized as the norm rather than an exception, but existing neuropathological assessment tools do not capture the complexity of concurrent co-pathologies. Characterization of this co-pathology is critical, as it has the potential to identify synergistic mechanisms. We developed a hierarchical cytoarchitectural classification system, which we applied to an autopsy series of military veterans with parkinsonism (n = 26), focusing on Lewy and neurofibrillary pathologies. We defined co-pathology as Type A (co-morbid), Type B (co-regional), Type C (co-cellular), or Type D (co-aggregate). The regional distributions of each co-pathology subtype were assessed using double-label immunohistochemistry in the frontal cortex, hippocampal formation, and midbrain. The frontal cortex demonstrated only subtypes A-C (no co-aggregates), whereas the midbrain and hippocampus showed all subtypes of copathology (A-D). In summary, we show marked differences in the prevalence and levels of mixed α-synuclein and tau pathology in this cohort. Our classification system has the potential to be applied broadly for the study of co-pathology in neurodegenerative disorders.","journal":"Journal of Neuropathology & Experimental Neurology","year":2025,"id":587646,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373084,"name":"Klaudia Laborc","orcid":null,"position":1,"is_corresponding":false},{"id":990860,"name":"Claudia De Sanctis","orcid":"0000-0002-9318-7323","position":2,"is_corresponding":false},{"id":1093967,"name":"Emma L Thorn","orcid":"0009-0007-3875-7542","position":3,"is_corresponding":false},{"id":282012,"name":"Adam O. Goldstein","orcid":"0000-0002-0664-235X","position":4,"is_corresponding":false},{"id":943872,"name":"Alessandra Cervera","orcid":null,"position":5,"is_corresponding":false},{"id":1503699,"name":"Dalilah F Quintana Mora","orcid":null,"position":6,"is_corresponding":false},{"id":1503700,"name":"Yolfrankcis Mendez","orcid":null,"position":7,"is_corresponding":false},{"id":1503701,"name":"Anya McGoldrick","orcid":null,"position":8,"is_corresponding":false},{"id":1399707,"name":"Lily Yu-Chia Chiu","orcid":null,"position":9,"is_corresponding":false},{"id":1503702,"name":"Quazi I Hossain","orcid":null,"position":10,"is_corresponding":false},{"id":1455066,"name":"Stephanie McQuillan","orcid":null,"position":11,"is_corresponding":false},{"id":1503703,"name":"Kourtni Lind-Watson","orcid":null,"position":12,"is_corresponding":false},{"id":308291,"name":"Jamie M. Walker","orcid":"0000-0003-1263-7394","position":13,"is_corresponding":false},{"id":1503704,"name":"R. Dale Walker","orcid":null,"position":14,"is_corresponding":false},{"id":1093966,"name":"Melissa J. Nirenberg","orcid":"0000-0003-3892-6733","position":15,"is_corresponding":false},{"id":308308,"name":"John F. Crary","orcid":"0000-0002-0556-293X","position":16,"is_corresponding":false},{"id":1503698,"name":"Victoria G Flores Almazan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41475018","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":[]}