Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests

作者：Nicolas R Barthélemy, Gemma Salvadó, Suzanne E. Schindler, Yingxin He, Shorena Janelidze, Lyduine E. Collij, Benjamin Saef, Rachel L. Henson, Charles D. Chen, Brian A. Gordon, Yan Li, Renaud La Joie, Tammie L.S. Benzinger, John C. Morris, Niklas Mattsson, Sebastian Palmqvist, Rik Ossenkoppele, Gil D. Rabinovici, Erik Stomrud, Randall J. Bateman, Oskar Hansson · 发表于：Nature Medicine · 年份：2024 · DOI：10.1038/s41591-024-02869-z · 被引用次数：447 · 研究领域：Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments、Advanced Neuroimaging Techniques and Applications

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n = 1,422) and the US Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) cohort (n = 337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using positron emission tomography (PET) imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area under the curve (AUC) for both between 0.95 and 0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired subcohorts (BioFINDER-2: n = 720; Knight ADRC: n = 50), plasma %p-tau217 had an accuracy, a positive predictive value and a...