A head-to-head comparison of multiple amyloid PET radiotracers for Down syndrome clinical trials.

Abstract

Adults with Down syndrome carry high risk of developing Alzheimer's disease and efforts to include this population in clinical trials remain limited. A barrier to recruitment for anti-amyloid trials includes the availability of the same amyloid PET radiotracer to multiple treatment centers. 237 adults with Down syndrome from the Trial-Ready Cohort - Down syndrome and Alzheimer Biomarker Consortium - Down syndrome studies were imaged using T1-w MRI and using PET images of PiB, Florbetapir (FBP), NAV4694 (NAV) or Flutemetamol (FMM) to screen for amyloid plaque (Aβ) burden. PiB displayed the largest effect size to measure amyloid change while FBP had a small effect size. NAV and PiB, which are structurally similar compounds, displayed similar sensitivity to measure longitudinal amyloid increase. The estimated age at amyloid onset showed no significant difference between PiB, FBP, NAV or FMM. The findings suggest that different amyloid PET radiotracers provide consistent estimates of amyloid onset age for adults with Down syndrome. Multicenter studies of Alzheimer's disease therapeutics can utilize multiple amyloid PET radiotracers to facilitate recruitment, however, PiB and NAV displayed the greatest sensitivity to detect longitudinal change.