The prognostic value of blood-based p-tau217 levels on progression to clinical impairment
Buckley, R. F.; Townsend, D. L.; Birkenbihl, C. J.; Cuppels, M.; Coughlan, G. T.; Seto, M. T.; Brown, J. A.; Properzi, M. J.; Honig, M. C.; Li, A.; Schultz, A. P.; Chhatwal, J.; Yang, H.-S.; Arnold, S.; Kivisakk, P.; James, B. D.; O'Bryant, S.; Rissman, R. A.; Petersen, M.; Caldwell, J. Z. K.; Betthauser, T.; Oomens, J. E.; Carrigan, M.; Healy, B.; Garcia Condado, J.; Johnson, S.; Yau, W.-Y.; Langford, O.; Farrell, M.; Amariglio, R. E.; Rentz, D. M.; Papp, K. V.; Hohman, T. J.; Donohue, M.; Aisen, P. S.; Johnson, K. A.; Sperling, R. A.
Show abstract
Plasma p-tau217 closely tracks amyloid-{beta} (A{beta}) pathology, yet its ability to predict long-term clinical progression in cognitively unimpaired (CU) adults remains uncertain. We analyzed harmonized data from 2,705 CU participants (Agemean=69.8{+/-}7years; Female=63%) across six longitudinal cohorts with up to 13.5 years of follow-up. Cox models evaluated associations between p-tau217 and progression to a clinical diagnosis of cognitive impairment, while natural cubic spline models assessed associations with longitudinal decline on a cognitive composite. Higher p-tau217 was associated with increased risk of progression (hazard-ratio[HR]=1.38; 95%CI:1.31-1.44), independent of demographics and APOE{varepsilon}4, and in models with A{beta}-PET (HR=1.30; 95%CI:1.23-1.38). Very high p-tau217 levels (>2.5SD) were associated with 61%[95%CI:53-68%] absolute risk of progression over 10 years. Elevated p-tau217 associated with accelerated cognitive decline, both independent of, and synergistic with, greater A{beta}-PET. These findings establish plasma p-tau217 as a robust prognostic marker in preclinical AD and support its value in future individualized risk prediction.
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