{"doi":"10.1101/2024.12.05.625499","title":"Peripheral immune cell response to stimulation stratifies Parkinson’s disease progression from prodromal to clinical stages","abstract":"Abstract The motor stage of idiopathic Parkinson’s disease (iPD) can be preceded for years by a prodromal stage characterized by non-motor symptoms like REM sleep behavior disorder (RBD). Here, we show that multiple stages of iPD, including the pre-motor prodromal stage, can be stratified according to the inflammatory and immunometabolic responses to stimulation of peripheral blood mononuclear cells ex vivo . We identified increased stimulation-dependent secretion of TNF, IL-1β, and IL-8 in monocytes from RBD patients and showed diminished proinflammatory cytokine secretion in monocytes and T cells in early and moderate stages of PD. Mechanistically, immune activation revealed deficits in CD8 + T-cell mitochondrial health in moderate PD, and relative mitochondrial health in CD8 + T cells was positively correlated with stimulation-dependent T-cell cytokine secretion across the PD spectrum. Dysregulated immunometabolism may drive peripheral inflammation and PD progression, and ex vivo stimulation-based assays have potential to reveal novel biomarkers for patient stratification and progression with immune endophenotypes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":492562,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1338799,"name":"Ann M. Titus","orcid":"0000-0002-1293-1350","position":1,"is_corresponding":false},{"id":1074765,"name":"Hannah A. Staley","orcid":"0009-0001-8284-6178","position":2,"is_corresponding":false},{"id":1339290,"name":"Stephan D. Alvarez","orcid":null,"position":3,"is_corresponding":false},{"id":1339291,"name":"Savanna Mahn","orcid":null,"position":4,"is_corresponding":false},{"id":348671,"name":"Nikolaus R. McFarland","orcid":"0000-0002-8699-8857","position":5,"is_corresponding":false},{"id":1172543,"name":"Rebecca Wallings","orcid":"0000-0003-3878-291X","position":6,"is_corresponding":false},{"id":77489,"name":"Malú G. Tansey","orcid":"0000-0002-1719-4708","position":7,"is_corresponding":false},{"id":1074764,"name":"Julian R Mark","orcid":"0000-0003-4152-7725","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:56.210382Z","pmid":"39677794","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":[]}