{"doi":"10.1093/brain/awac175","title":"Ante-mortem plasma phosphorylated tau (181) predicts Alzheimer’s disease neuropathology and regional tau at autopsy","abstract":"Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau181) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer's disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau181 as an accurate and reliable biomarker of Alzheimer's disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer's Disease Research Center who had a plasma sample analysed for phosphorylated-tau181 between 2008 and 2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau181 was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer's disease. Average time between blood draw and death was 5.6 years (standard deviation = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau181 concentrations were associated with increased odds for having autopsy-confirmed Alzheimer's disease [AUC = 0.82, OR = 1.07, 95% CI = 1.03-1.11, P < 0.01; phosphorylated-tau standardized (z-transformed): OR = 2.98, 95% CI = 1.50-5.93, P < 0.01]. Higher plasma phosphorylated-tau181 levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02-1.09, P < 0.01) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03-1.06, P < 0.05). The association between plasma phosphorylated-tau181 and Alzheimer's disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02-1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01-1.10). There was higher discrimination accuracy for Alzheimer's disease when blood draw occurred in years closer to death; however, higher plasma phosphorylated-tau181 levels were associated with Alzheimer's disease even when blood draw occurred >5 years from death. Ante-mortem plasma phosphorylated-tau181 concentrations were associated with Alzheimer's disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer's disease. These findings support plasma phosphorylated-tau181 as a scalable biomarker for the detection of Alzheimer's disease.","journal":"Brain","year":2022,"id":248906,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":273463,"name":"Hugo J. Aparicio","orcid":"0000-0001-8584-1455","position":1,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":2,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":3,"is_corresponding":false},{"id":241104,"name":"Nicholas J. Ashton","orcid":"0000-0002-3579-8804","position":4,"is_corresponding":false},{"id":241105,"name":"Thomas K. Karikari","orcid":"0000-0003-1422-4358","position":5,"is_corresponding":false},{"id":271279,"name":"Yorghos Tripodis","orcid":"0000-0003-2190-7608","position":6,"is_corresponding":false},{"id":874869,"name":"Brett Martin","orcid":"0009-0006-9610-0672","position":7,"is_corresponding":false},{"id":304493,"name":"Joseph Palmisano","orcid":"0000-0001-6000-3025","position":8,"is_corresponding":false},{"id":306391,"name":"Michael A. Sugarman","orcid":null,"position":9,"is_corresponding":false},{"id":888500,"name":"Brandon Frank","orcid":"0000-0002-0548-9074","position":10,"is_corresponding":false},{"id":304494,"name":"Eric Steinberg","orcid":"0000-0002-6479-3623","position":11,"is_corresponding":false},{"id":769129,"name":"Katherine W. Turk","orcid":"0000-0002-6833-5494","position":12,"is_corresponding":false},{"id":67995,"name":"Andrew E. Budson","orcid":"0000-0002-2913-0015","position":13,"is_corresponding":false},{"id":227481,"name":"Rhoda Au","orcid":"0000-0001-7742-4491","position":14,"is_corresponding":false},{"id":297230,"name":"Lee E. Goldstein","orcid":"0000-0001-8419-9800","position":15,"is_corresponding":false},{"id":562002,"name":"Gyungah Jun","orcid":"0000-0002-3230-8697","position":16,"is_corresponding":false},{"id":291833,"name":"Neil W. Kowall","orcid":"0000-0002-6624-0213","position":17,"is_corresponding":false},{"id":19615,"name":"Ronald Killiany","orcid":"0000-0003-4740-2181","position":18,"is_corresponding":false},{"id":493568,"name":"Wei Qiao Qiu","orcid":"0000-0002-2082-2410","position":19,"is_corresponding":false},{"id":304496,"name":"Robert A. Stern","orcid":"0000-0002-5008-077X","position":20,"is_corresponding":false},{"id":261843,"name":"Jesse Mez","orcid":"0000-0003-1438-5442","position":21,"is_corresponding":false},{"id":271280,"name":"Ann C. McKee","orcid":"0000-0003-2961-7488","position":22,"is_corresponding":false},{"id":271281,"name":"Thor D. Stein","orcid":"0000-0001-6954-4477","position":23,"is_corresponding":false},{"id":68034,"name":"Michael L. 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