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Neurodegenerative Disease Research","award":["JPND2021-00694"],"award-info":[{"award-number":["JPND2021-00694"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, the UK Dementia Research Institute at UCL","award":["UKDRI-1003"],"award-info":[{"award-number":["UKDRI-1003"]}],"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:p>\n                    Phosphorylated-tau 217 (pTau217) is currently the most promising blood-based biomarker for accurately detecting Alzheimer\u2019s disease (AD) pathology. However, interference from peripheral tau species in the kidneys or peripheral nerves can hinder diagnostic precision. Recently developed brain-derived pTau217 (BD-pTau217) assays emerge as highly specific tools for detecting AD-related pathological changes in the brain. In this study, we conducted a head-to-head comparison of the NULISAqpcr BD-pTau217 assay and Simoa ALZpath total p-Tau217 assay in two independent, amyloid-PET\u2013characterized Chinese cohorts. Our results demonstrate a strong correlation between BD-pTau217 and total pTau217 (\u03c1 = 0.89 to 0.90), with BD-pTau217 showing significantly reduced interference from kidney dysfunction, as evidenced by weaker associations with blood levels of urea (\u03c1\n                    <jats:sub>BD-pTau217<\/jats:sub>\n                    = 0.02 to 0.06, \u03c1\n                    <jats:sub>Total-pTau217<\/jats:sub>\n                    = 0.06 to 0.12) and creatinine (\u03c1\n                    <jats:sub>BD-pTau217<\/jats:sub>\n                    = 0.03 to 0.08, \u03c1\n                    <jats:sub>Total-pTau217<\/jats:sub>\n                    = 0.16 to 0.18). Moreover, BD-pTau217 is more strongly associated with amyloid-PET Centiloid values (\u03c1\n                    <jats:sub>BD-pTau217<\/jats:sub>\n                    = 0.78 to 0.80, \u03c1\n                    <jats:sub>Total-pTau217<\/jats:sub>\n                    = 0.74 to 0.77) and exhibits superior classification performance for amyloid-\u03b2 (A\u03b2) pathology (area under the curve [AUC]\n                    <jats:sub>BD-pTau217<\/jats:sub>\n                    = 0.96 to 0.98, AUC\n                    <jats:sub>Total-pTau217<\/jats:sub>\n                    = 0.94 to 0.97). Furthermore, BD-pTau217 outperforms total pTau217 for identifying tau-positive individuals within the A\u03b2-positive group (AUC\n                    <jats:sub>BD-pTau217<\/jats:sub>\n                    = 0.89, AUC\n                    <jats:sub>Total-pTau217<\/jats:sub>\n                    = 0.78), facilitating more accurate disease staging. These findings underscore BD-pTau217 as a highly sensitive and specific blood-based biomarker for AD that has significant potential for early detection, precise classification, and staging of AD-related brain pathology in clinical practice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2536792123","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T20:10:06Z","timestamp":1772482206000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification"],"prefix":"10.1073","volume":"123","author":[{"given":"Yuanbing","family":"Jiang","sequence":"first","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology","place":["Hong Kong Special Administrative Region, China"]},{"name":"InnoHK Hong Kong Center for Neurodegenerative Diseases","place":["Hong Kong Special Administrative Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology","place":["Hong Kong Special Administrative Region, China"]},{"name":"InnoHK Hong Kong Center for Neurodegenerative Diseases","place":["Hong Kong Special Administrative Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengjie","family":"Xia","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology","place":["Hong Kong Special Administrative Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Wa","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology","place":["Hong Kong Special Administrative Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily K. W.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology","place":["Hong Kong Special Administrative Region, China"]},{"name":"InnoHK Hong Kong Center for Neurodegenerative Diseases","place":["Hong Kong Special Administrative Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny C.","family":"Ip","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology","place":["Hong Kong Special Administrative Region, China"]},{"name":"InnoHK Hong Kong Center for Neurodegenerative Diseases","place":["Hong Kong Special Administrative Region, China"]},{"name":"Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, Hong Kong University of Science and Technology Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu Man","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen Elizabeth Hospital, Hospital Authority","place":["Hong Kong Special Administrative Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L. 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