Poster Presentation Australian and New Zealand Society for Geriatric Medicine Annual Scientific Meeting 2026

Prognostic Models for Development of Elevated Plasma P-tau217 in Cognitively Unimpaired Alzheimer’s Disease: Insights from A4/LEARN. (#265)

Roy Yaari 1 , Nalin Payakachat 1 , Nicolae Done 2 , Urvi Desai 2 , Yun-Fei Chen 1 , Chia-Lun Liu 2 , Pete T Zuckerman 2 , Zachary T Sheff 1 , Jolanda Muenzel 1 , Karen C Holdridge 1 , Dulanji C Kuruppu 1 , Michael S Rafii 3 , Noam Kirson 2 , Emma Devenney 4 , Reisa Sperling 5
  1. Eli Lilly and Company, Indianapolis, IN, USA
  2. Analysis Group, Boston, MA, USA
  3. University of Southern California, Los Angeles, CA, USA
  4. Neuroscience Research Australia NeuRA, Sydney NSW, Australia
  5. Harvard Medical School, Boston, MA, USA

Introduction: Plasma P-tau217, a promising biomarker for Alzheimer's disease(AD) biomarker, facilitates early detection and monitoring.  Predicting elevated P-tau217 in cognitively unimpaired individuals could enhance diagnostics and trial enrichment strategies.

Objective: We developed five-year prognostic models for estimating risk of elevated plasma P-tau217.

Methods: This analysis utilised the A4 and LEARN studies involving cognitively unimpaired adults aged 65-85 years with amyloid positron emission tomography results at baseline. Participants with baseline plasma P-tau217 below the highest tertile were analyzed for time to elevation. Random survival forests identified predictors using Cox models. Discrimination and calibration were assessed using Harrell’s C-index, AUC and IBS. Kaplan–Meier analyses evaluated the ability of the models to meaningfully separate risk groups over five years.

Results: Of 1,707 participants, 881 were included (A4:636, LEARN:245). Mean age was 70.6 years, 62.0% were female, and 47.1% carried at least one APOE ε4 allele. Over a median follow-up of 4.2 years, 22.0% developed elevated plasma P-tau217. Baseline plasma P-tau217 was the most important predictor. The model with baseline plasma P-tau217, age, and education performed better (C-Index=0.822; AUC=0.759; IBS=0.069) than models without P-tau217 data.

Conclusion: Prognostic models can stratify five-year risk of elevated P-tau217, guiding diagnostics and AD trial enrichment strategies. The model included P-tau217 yielded the best performance, compared to models without P-tau217.