Plasma p-tau217 measured by the Elecsys automated immunoassay: Prospective validation in a heterogeneous memory clinic cohort

Background Plasma phosphorylated tau at threonine 217 (p-tau217) has emerged as a leading blood-based biomarker for the diagnosis of Alzheimer's disease (AD) and can be measured using fully automated, random-access platforms. The Elecsys plasma p-tau217 assay requires further validation, particularly in heterogenous populations seen in memory clinics. Objective To validate plasma p-tau217 in comparison with p-tau181 and to evaluate its association with other soluble core 1 AD biomarkers, as well as markers of neurodegeneration and neuroinflammation. Methods Biobank data from two prospective blood-based biomarkers validation studies were analyzed. Cerebrospinal fluid (CSF) p-tau181/Aβ 42 ratio served as the reference standard for AD diagnosis. The diagnostic performance of plasma p-tau217 and p-tau181 was compared. In patients with AD, p-tau217 was further evaluated for its association with CSF (Aβ 42 /Aβ 40 ratio, p-tau181, t-tau) and plasma APOE ε4 protein (APOE ε4p), NfL (neurofilament light chain), GFAP (glial fibrillary acidic protein) biomarkers. Results Among 303 patients with mild cognitive impairment or mild dementia, plasma p-tau217 outperformed plasma p-tau181 (AUC 0.93 versus 0.87). By the two threshold diagnostic strategy, an upper cutoff (>0.312 pg/mL, specificity 95%) and a lower cutoff (<0.177 pg/mL, sensitivity 95%) were established, with 27% of cases falling into an indeterminate range. Plasma p-tau217 showed strong correlations with CSF Aβ 42 /Aβ 40 and p-tau181/Aβ 42 ratios, as well as with plasma GFAP, and only moderate correlations with CSF t-tau and p-tau181, and plasma NfL. Conclusions Plasma p-tau217 measured using Elecsys demonstrates good diagnostic performance and strong associations with other soluble Core 1 AD and neuroinflammation biomarkers.