{"doi":"10.1002/ana.27003","title":"Plasma pTau181 Reveals a Pathological Signature that Predicts Cognitive Outcomes in Lewy Body Disease","abstract":"OBJECTIVE: To determine whether plasma phosphorylated-Tau181 (pTau181) could be used as a diagnostic biomarker of concurrent Alzheimer's disease neuropathologic change (ADNC) or amyloidosis alone, as well as a prognostic, monitoring, and susceptibility/risk biomarker for clinical outcomes in Lewy body disease (LBD). METHODS: We studied 565 participants: 94 LBD with normal cognition, 83 LBD with abnormal cognition, 114 with Alzheimer's disease, and 274 cognitively normal. Plasma pTau181 levels were measured with the Lumipulse G platform. Diagnostic accuracy for concurrent ADNC and amyloidosis was assessed with Receiver Operating Characteristic curves in a subset of participants with CSF pTau181/Aβ42, and CSF Aβ42/Aβ40 or amyloid-β PET, respectively. Linear mixed effects models were used to examine the associations between baseline and longitudinal plasma pTau181 levels and clinical outcomes. RESULTS: Plasma pTau181 predicted concurrent ADNC and amyloidosis in LBD with abnormal cognition with 87% and 72% accuracy, respectively. In LBD patients with abnormal cognition, higher baseline plasma pTau181 was associated with worse baseline MoCA and CDR-SB, as well as accelerated decline in CDR-SB. Additionally, in this group, rapid increases in plasma pTau181 over 3 years predicted a faster decline in CDR-SB and memory. In LBD patients with normal cognition, there was no association between baseline or longitudinal plasma pTau181 levels and clinical outcomes; however, elevated pTau181 at baseline increased the risk of conversion to cognitive impairment. INTERPRETATION: Our findings suggest that plasma pTau181 is a promising biomarker for concurrent ADNC and amyloidosis in LBD. Furthermore, plasma pTau181 holds potential as a prognostic, monitoring, and susceptibility/risk biomarker, predicting disease progression in LBD. ANN NEUROL 2024;96:526-538.","journal":"Annals of Neurology","year":2024,"id":436862,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9258,"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":666595,"name":"Christina B. Young","orcid":"0000-0001-9535-2137","position":1,"is_corresponding":false},{"id":279146,"name":"Marian Shahid","orcid":"0000-0002-8515-3238","position":2,"is_corresponding":false},{"id":825459,"name":"Alena Smith","orcid":null,"position":3,"is_corresponding":false},{"id":279144,"name":"Edward N. Wilson","orcid":"0000-0003-0640-5247","position":4,"is_corresponding":false},{"id":1007050,"name":"Javier Ramos Benitez","orcid":"0000-0001-8893-0146","position":5,"is_corresponding":false},{"id":29925,"name":"Hillary Vossler","orcid":null,"position":6,"is_corresponding":false},{"id":296392,"name":"Melanie J. Plastini","orcid":"0000-0003-2011-7882","position":7,"is_corresponding":false},{"id":246337,"name":"Joseph R. Winer","orcid":"0000-0003-4069-3158","position":8,"is_corresponding":false},{"id":480574,"name":"Geoffrey A. Kerchner","orcid":"0000-0001-7674-0695","position":9,"is_corresponding":false},{"id":279150,"name":"Brenna Cholerton","orcid":"0000-0002-2139-987X","position":10,"is_corresponding":false},{"id":246389,"name":"Katrin I. Andreasson","orcid":"0000-0001-8391-4155","position":11,"is_corresponding":false},{"id":355540,"name":"Victor W. Henderson","orcid":"0000-0003-1198-9240","position":12,"is_corresponding":false},{"id":657859,"name":"Maya Yutsis","orcid":null,"position":13,"is_corresponding":false},{"id":107086,"name":"Thomas J. Montine","orcid":"0000-0002-1346-2728","position":14,"is_corresponding":false},{"id":51246,"name":"Lü Tian","orcid":"0000-0002-5893-0169","position":15,"is_corresponding":false},{"id":29931,"name":"Elizabeth C. Mormino","orcid":"0000-0002-4542-6537","position":16,"is_corresponding":false},{"id":279151,"name":"Kathleen L. Poston","orcid":"0000-0003-3424-7143","position":17,"is_corresponding":false},{"id":264832,"name":"Carla Abdelnour","orcid":"0000-0002-7636-9758","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:00:16.989773Z","pmid":"38888142","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":[]}