HAI Book 2025 - Flipbook - Page 557
Yang, Hyun-Sik
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Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ,
tau, and cognition in cognitively unimpaired older adults
Hyun-Sik Yang1,2,3, Juliana Anzai1,2, Wai-Ying Yau1,2,3, Andrea Román Viera1,2, Courtney Maa1,2,
Dylan Kirn1,2, Michael Properzi2, Aaron Schultz2,3, Michelle Farrell2,3, Heidi Jacobs2,3, Rachel
Buckley2,3, Kathryn Papp1,2,3, Gad Marshall1,2,3, Rebecca Amariglio1,2,3, Dorene Rentz1,2,3, Joel
Braunstein4, Keith Johnson1,2,3, Reisa Sperling1,2,3, Jasmeer Chhatwal1,2,3
Brigham and Women’s Hospital, Boston, MA, US
Massachusetts General Hospital, Boston, MA, US
3
Harvard Medical School, Boston, MA, US
4
C2N Diagnostics, St. Louis, MO, US
1
2
Background: Plasma phosphorylated tau 217 (pTau217) reflects the AD pathology burden, but its utility in
predicting longitudinal disease progression in cognitively unimpaired (CU) older adults remains unclear.
Methods: Baseline plasma %pTau217 (pTau217/non-phosphorylated-Tau217×100) from n=318 Harvard Aging Brain
Study participants (61% female, 81% white, follow-up 8.0±3.9 years, CU at baseline) was quantified by C2N
Diagnostics. We obtained annual Preclinical Alzheimer9s Cognitive Composite 5 (PACC5), and Pittsburgh
compound B (PiB) and flortaucipir (FTP) PET in Years 1 (baseline), 4, 6, 9, 12. We used cortical PiB DVR (Centiloid
[CL]), mesial temporal lobe (MTL), and temporal neocortical (NEO) FTP SUVR composites. Association between
%pTau217 and longitudinal A´, tau, and cognition were assessed using linear mixed effect models, accounting for
age, sex, APOE ε4, and education. A log-rank test assessed the
