학술논문
Potential Utility of Plasma P-Tau and Neurofilament Light Chain as Surrogate Biomarkers for Preventive Clinical Trials
Document Type
Author
Ferreira, P. C. L.; Ferrari-Souza, J. P.; Tissot, C.; Bellaver, B.; Leffa, D. T.; Lussier, F.; Povala, G.; Therriault, J.; Lessa Benedet, Andréa; Ashton, Nicholas J.; Cohen, A. D.; Lopez, O. L.; Tudorascu, D. L.; Klunk, W. E.; Soucy, J. P.; Gauthier, S.; Villemagne, V.; Zetterberg, Henrik, 1973; Blennow, Kaj, 1958; Rosa-Neto, P.; Zimmer, E. R.; Karikari, Thomas; Pascoal, T. A.; Alzheimers Dis, Neuroimaging
Source
NEUROLOGY. 101(1):38-45
Subject
Language
English
ISSN
0028-3878
Abstract
ObjectiveTo test the utility of longitudinal changes in plasma phosphorylated tau 181 (p-tau181) and neurofilament light chain (NfL) as surrogate markers for clinical trials targeting cognitively unimpaired (CU) populations.MethodsWe estimated the sample size needed to test a 25% drug effect with 80% of power at a 0.05 level on reducing changes in plasma markers in CU participants from Alzheimer's Disease Neuroimaging Initiative database.ResultsWe included 257 CU individuals (45.5% males; mean age = 73 [6] years; 32% & beta;-amyloid [A & beta;] positive). Changes in plasma NfL were associated with age, whereas changes in plasma p-tau181 with progression to amnestic mild cognitive impairment. Clinical trials using p-tau181 and NfL would require 85% and 63% smaller sample sizes, respectively, for a 24-month than a 12-month follow-up. A population enrichment strategy using intermediate levels of A & beta; PET (Centiloid 20-40) further reduced the sample size of the 24-month clinical trial using p-tau181 (73%) and NfL (59%) as a surrogate.DiscussionPlasma p-tau181/NfL can potentially be used to monitor large-scale population interventions in CU individuals. The enrollment of CU with intermediate A & beta; levels constitutes the alternative with the largest effect size and most cost-effective for trials testing drug effect on changes in plasma p-tau181 and NfL.