Abstract
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.