{"doi":"10.1093/brain/awaf135","title":"Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy","abstract":"Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by four-repeat (4R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brains of patients with neurodegenerative diseases, although a few reports have described their presence in the α-synucleinopathy Parkinson's disease (PD). To evaluate the cytotoxic T-cell response, serial sections spanning 120 μm of the SN were immunostained consecutively for phosphorylated tau (p-tau, AT8) or α-synuclein, cytotoxic T-cell marker and microglia marker HLA-DR. Sections were analysed with stereology software in 9 patients with PSP, 10 with PD and 6 healthy controls. We semiquantitatively scored CD8-positive cells in further brain regions. CD8 lymphocyte cell counts and microglial activation in the SN were higher in PSP than PD and controls. Furthermore, T-cell/neuron contact was observed in PSP. In multivariate models, CD8 counts were not predicted by disease duration, younger age at death or the amount of p-tau pathology. The SN and midbrain tegmentum showed more CD8 cells than the cortex. A more prominent nigral cytotoxic T-cell response in PSP than PD supports the suggestion that p-tau neuropathology in PSP might have potential relationships with autoimmune mechanisms.","journal":"Brain","year":2025,"id":512867,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"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":1036935,"name":"Shelley L. Forrest","orcid":"0000-0001-7863-5389","position":1,"is_corresponding":false},{"id":779632,"name":"Conor Fearon","orcid":"0000-0002-8172-6094","position":2,"is_corresponding":false},{"id":900879,"name":"Seojin Lee","orcid":"0000-0003-2827-1091","position":3,"is_corresponding":false},{"id":1373074,"name":"Samantha Knott","orcid":"0000-0002-2470-5553","position":4,"is_corresponding":false},{"id":771500,"name":"Jun Li","orcid":"0000-0001-6366-7564","position":5,"is_corresponding":false},{"id":245790,"name":"Susan H. Fox","orcid":"0009-0004-7568-1645","position":6,"is_corresponding":false},{"id":253935,"name":"Maria Carmela Tartaglia","orcid":"0000-0002-5944-8497","position":7,"is_corresponding":false},{"id":17424,"name":"Anthony E. Lang","orcid":"0000-0003-1229-3667","position":8,"is_corresponding":false},{"id":227415,"name":"Gábor G. Kovács","orcid":"0000-0003-3841-5511","position":9,"is_corresponding":false},{"id":900877,"name":"Blas Couto","orcid":"0000-0002-3512-7488","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:11.233009Z","pmid":"40233181","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":[]}