H Y Yang, Juliana A. U. Anzai, Wai‐Ying Wendy Yau, Brian C. Healy, Andrea M. Román Viera, Courtney Maa, Dylan Kirn, Michael J Properzi, Jean-Pierre Bellier, Aaron P. Schultz, M. Farrell, Heidi I.L. Jacobs, Rachel F. Buckley, Kathryn V. Papp, Gad A. Marshall, Rebecca E. Amariglio, Dorene M. Rentz, Lei Liu, Dennis J. Selkoe, Philip B. Verghese, Joel B. Braunstein, Keith A. Johnson, Reisa A. Sperling, Jasmeer P. Chhatwal
Plasma phosphorylated tau 217 (pTau217) is an excellent biomarker of Alzheimer’s disease (AD) pathology, but it remains uncertain whether pTau217 can predict amyloid-β (Aβ) and tau accumulation prior to Aβ positron emission tomography (PET) positivity. Here, we leverage data from a well-characterized prospective cohort of cognitively unimpaired older adults to examine mass spectrometry-based plasma %pTau217 (pTau217/non-phosphorylated-Tau217×100) relative to changes in Aβ/tau PET and cognition. A higher baseline %pTau217 was associated with faster Aβ and tau accumulation on PET, which then led to greater cognitive decline. Among individuals Aβ PET-negative at baseline, higher %pTau217 levels presaged increases in Aβ and tau PET signals. Together, our results suggest that very low %pTau217 in cognitively unimpaired older adults is associated with a minimal risk of AD pathology accumulation and cognitive decline. Plasma phosphorylated tau 217 levels predict future accumulation of Alzheimer’s disease pathology in cognitively unimpaired older adults without elevated brain amyloid-β (“A-”) on positron emission tomography.