For the roughly six million people worldwide living with Down syndrome — nearly all of whom face near-certain Alzheimer's disease risk by their 40s and 50s — reliable early detection has long been an unmet clinical need. Standard cognitive assessments are confounded by intellectual disability, and PET imaging remains expensive and inaccessible. A blood-based alternative that performs with high accuracy would fundamentally change how clinicians approach this population.
This exploratory study evaluated two commercially available, fully automated plasma phospho-tau217 (p-tau217) assays in 39 participants from the NIH Trial Ready Cohort for Down Syndrome (TRC-DS). Amyloid burden confirmed by PET imaging (threshold: 18 centiloids) served as the gold standard. The Fujirebio Lumipulse immunoassay achieved an area under the curve (AUC) of 0.94, with 88% sensitivity and 90% specificity. The C2N Diagnostics PrecivityAD2 mass spectrometry platform reached an AUC of 0.91, with comparable sensitivity and 94% specificity. Both platforms delivered overall accuracy above 90% — performance on par with composite multi-biomarker panels.
These findings matter for several reasons beyond their face-value accuracy numbers. In the broader Alzheimer's biomarker field, p-tau217 has emerged as one of the most diagnostically precise single markers in neurotypical populations, and this study extends that signal into a genetically distinct, high-risk group where the underlying amyloid cascade is driven by APP triplication rather than sporadic mechanisms. The concordance between two technically distinct platforms — immunoassay versus mass spectrometry — strengthens confidence that the signal reflects genuine biology rather than platform artifact. However, critical limitations cannot be overlooked: the n=39 cohort is small, the study is cross-sectional and exploratory by design, and cutpoint optimization via Youden index on the same sample risks overfitting. Validation in larger, longitudinal DS cohorts is essential before clinical translation. That said, for a population historically excluded from AD blood biomarker research, these preliminary AUCs represent a meaningful step toward accessible, scalable screening.