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. P-tau217 is a promising blood-based biomarker for Alzheimer’s dementia (AD) in the clinical stage. In this prospective cohort study, it showed better performance in the prodromal than in the preclinical stage up to 17 years before diagnosis. In a subgroup analysis, the Aß misfolding biomarker showed higher discriminative ability in the preclinical stage compared to p-tau217. A prediction model including p-tau217, NfL, GFAP, Aß misfolding as well as basic demographic and genetic information reached an AUC of 0.86 for AD over the entire follow-up period. In a subgroup analysis, the Aß misfolding biomarker showed higher discriminative ability in the preclinical stage compared to p-tau217. A prediction model including p-tau217, NfL, GFAP, Aß misfolding as well as basic demographic and genetic information reached an AUC of 0.86 for AD over the entire follow-up period. P-tau217 is a promising blood-based biomarker for Alzheimer’s dementia (AD) in the clinical stage. In this prospective cohort study, it showed better performance in the prodromal than in the preclinical stage up to 17 years before diagnosis.