Exploring automated plasma phospho-tau217 assays for the diagnosis of Down syndrome-related Alzheimer’s disease

BACKGROUND: Individuals with Down syndrome (DS) develop a genetic form of Alzheimer's disease (AD) due to an extra copy of chromosome 21, which contains the APP gene. Blood-based biomarkers of AD are becoming increasingly adopted in research and clinical practice. These tests hold promise for diagnosing AD in DS once validated. METHODS: In this exploratory study, we assessed plasma phospho-tau217 (p-tau217) in participants (n = 39) from the NIH Trial Ready Cohort - Down syndrome (TRC-DS), using predefined amyloid-PET cutoffs. Plasma p-tau217 was measured via two fully automated assays: C2N Diagnostics' PrecivityAD2 mass spectrometry and Fujirebio's Lumipulse immunoassay. The primary outcome was β-amyloid AD pathology, defined by amyloid PET > 18 centiloids. RESULTS: Both p-tau217 assays showed high accuracy: AUCs of 0.94 (95% CI 0.84, 1.00) for Lumipulse and 0.91 (95% CI 0.77, 1.00) for C2N, with sensitivities of 0.88 (95% CI 0.62, 1.00), specificities of 0.90 (95% CI 0.77, 1.00) and 0.94 (95% CI 0.84, 1.00), and overall accuracies of 0.90 (95% CI 0.79, 0.97) and 0.92 (95% CI 0.82-1.00), respectively, when using maximized Youden index cutpoints. CONCLUSION: These preliminary results are comparable to composite plasma measures. In summary, automated p-tau217 tests offer strong potential for routine AD screening in individuals with DS.