Predictive value of plasma p-tau217 for Alzheimer's dementia compared to other blood-based biomarkers

Phosphorylated-tau (p-tau217) is a promising blood-based biomarker for Alzheimer's dementia (AD) in clinical settings. However, research from prospective cohort studies is sparse. We measured plasma p-tau217 levels in baseline blood samples of 779 participants in a population-based cohort of older adults followed over 17 years. Associations with AD were assessed and compared to those with previous measurements of p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Comparisons to the amyloid beta (Aβ) misfolding biomarker were performed in a subgroup analysis. P-tau217, NfL and GFAP showed strong associations with AD risk, especially within the first 9 years of follow-up, outperforming p-tau181. Over the later years of follow-up, the predictive accuracy of p-tau217 was significantly reduced. In contrast, the Aβ misfolding biomarker demonstrated superior performance especially as a preclinical indicator of the risk of AD many years before diagnosis. The combination of p-tau217 with NfL, GFAP, basic demographic and genetic information, as well as the misfolding biomarker yielded an AUC 0.86 for AD diagnoses over the entire 17-year follow-up period.