Accuracy and clinical applicability of plasma tau 181 and 217 for Alzheimer's disease diagnosis in a memory clinic cohort.

Plasma tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217) have demonstrated high accuracy for Alzheimer's disease (AD) diagnosis, defined by CSF/PET amyloid beta (Aβ) positivity, but most studies have been performed in research cohorts, limiting their generalizability. We studied plasma p-tau217 and p-tau181 for CSF Aβ status discrimination in a cohort of consecutive patients attending an academic memory clinic in Spain (July 2019-June 2024). All patients had CSF AD biomarkers performed as part of their routine clinical assessment. Aβ positivity was defined with a local cut-off of CSF Aβ _1-42  < 600 pg/mL; in patients with borderline Aβ _1-42 values or when there was a mismatch between the Aβ and the T status (T + if CSF p-tau181 ≥ 65 pg/mL), a ratio Aβ _1-42 /Aβ _1-40  < 0.07 was used. Plasma p-tau217 and p-tau181 were measured retrospectively, from blood samples collected at first visit, with Fujirebio Lumipulse and Quanterix Simoa assays, respectively. We included 468 patients (mean age 67 years, 50% female, 61% Aβ positive). Plasma p-tau217 outperformed plasma p-tau181 in discriminating CSF Aβ status (AUC 0.95 vs 0.90, p = 0.005). A 97.5% sensitivity and specificity plasma p-tau217 algorithm, classifying patients into three groups of Aβ probability (Low, Intermediate and High), resulted in 67% of patients in the Low and High groups, having their Aβ status predicted (as negative and positive, respectively) with 96% accuracy. The remaining 33% in the Intermediate group were candidates to undergo CSF/PET testing. A model with a 10% variation in p-tau217 levels yielded small changes in accuracy (95%). In conclusion, plasma p-tau217 could have discriminated CSF Aβ status in two-thirds of patients with very high accuracy in a memory clinic cohort. These results support the implementation of plasma p-tau217 as an initial diagnostic tool in memory clinics for AD diagnosis, reducing the need for more invasive/expensive testing.
Competing Interests: Declarations. Conflicts of interest: RSV has served in Advisory Boards Meetings for Wave Life Sciences, Ionis, and Novo Nordisk and received personal fees for participating in educational activities from Janssen, Roche Diagnostics, and Neuroxpharma and funding to her institution for Investigator Initiated studies from Biogen and Sage Pharmaceuticals. The rest of the authors report no relevant disclosures. Ethical approval: The study protocol was approved by the Hospital Clínic de Barcelona Research Ethics Committee (HCB/2019/0600).
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