{"doi":"10.1002/acn3.51695","title":"Plasma phosphorylated tau181 predicts cognitive and functional decline","abstract":"OBJECTIVE: To determine if plasma tau phosphorylated at threonine 181 (p-tau181) distinguishes pathology-confirmed Alzheimer's disease (AD) from normal cognition (NC) adults, to test if p-tau181 predicts cognitive and functional decline, and to validate findings in an external cohort. METHODS: Thirty-one neuropathology-confirmed AD cases, participants with clinical diagnoses of mild cognitive impairment (MCI, N = 91) or AD dementia (N = 64), and NC (N = 241) had plasma collected at study entry. The clinical diagnosis groups had annual cognitive (Mini-Mental State Examination, MMSE) and functional (Clinical Dementia Rating Scale, CDR) measures. NC (N = 70), MCI (N = 75), and AD dementia (N = 50) cases from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used as a validation cohort. Plasma p-tau181 was measured using the Quanterix SiMoA HD-X platform. RESULTS: Plasma p-tau181 differentiated pathology-confirmed AD from NC with negative amyloid PET scans with an AUC of 0.93. A cut point of 3.44 pg/mL (maximum Youden Index) had a sensitivity of 0.77, specificity of 0.96. p-Tau181 values above the cut point were associated with the faster rate of decline in MMSE in AD dementia and MCI and a shorter time to a clinically significant functional decline in all groups. In a subset of MCI cases from ADNI, p-tau181 values above the cut point associated with faster rate of decline in MMSE, and a shorter time to a clinically significant functional decline and conversion to dementia. INTERPRETATION: Plasma p-tau181 differentiates AD pathology cases from NC with high accuracy. Higher levels of plasma p-tau181 are associated with faster cognitive and functional decline.","journal":"Annals of Clinical and Translational Neurology","year":2022,"id":243464,"datarank":0.9789296511412964,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.4456274419178842,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.4456274419178842,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":27,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7215,"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":622428,"name":"Teresa Waligórska","orcid":null,"position":1,"is_corresponding":false},{"id":227428,"name":"Sharon X. Xie","orcid":"0000-0002-7886-4103","position":2,"is_corresponding":false},{"id":230030,"name":"Ilya M. Nasrallah","orcid":"0000-0003-2346-7562","position":3,"is_corresponding":false},{"id":750910,"name":"Katheryn A Q Cousins","orcid":"0000-0003-1879-2766","position":4,"is_corresponding":false},{"id":27606,"name":"John Q. Trojanowski","orcid":"0000-0002-9239-8794","position":5,"is_corresponding":false},{"id":58510,"name":"Murray Grossman","orcid":"0000-0002-7447-6218","position":6,"is_corresponding":false},{"id":227417,"name":"David J. Irwin","orcid":"0000-0002-5599-5098","position":7,"is_corresponding":false},{"id":80309,"name":"Daniel Weintraub","orcid":"0000-0003-0633-7168","position":8,"is_corresponding":false},{"id":107087,"name":"Edward B. Lee","orcid":"0000-0002-4589-1180","position":9,"is_corresponding":false},{"id":230045,"name":"David A. Wolk","orcid":"0000-0002-3554-3481","position":10,"is_corresponding":false},{"id":76194,"name":"Alice S. Chen-Plotkin","orcid":"0000-0002-3387-2038","position":11,"is_corresponding":false},{"id":27605,"name":"Leslie M. Shaw","orcid":"0000-0002-7650-1210","position":12,"is_corresponding":false},{"id":29928,"name":"the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":13,"is_corresponding":false},{"id":573957,"name":"Thomas F. Tropea","orcid":"0000-0003-0766-1496","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:16.032700Z","pmid":"36518085","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":[]}