PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations

Abstract

Introduction: Individuals with Down syndrome (DS) have a high prevalence of Alzheimer's disease (AD) and reveal an earlier age of amyloid beta (Aβ) onset compared to sporadic AD. Differences in amyloid accumulation rates between DS and sporadic AD populations have not been established.

Methods: Participants with ≥ 3 [C-11]PiB scans (spanning > 6 years) and transitioning to Aβ+ were included, resulting in 20 DS and 23 neurotypical (NT) participants. Amyloid accumulation was compared using global standardized uptake value ratio (SUVR) for Aβ deposition, with individual growth rates (r) estimated using the logistic growth model ( $SUVR\left(t\right)=SUV{R}_{BL}+\frac{K}{1+e^{-r\left(t-t_{50}\right)}}$ ).

Results: The average growth rate in the DS cohort was 0.28 (0.08)/year versus 0.20 (0.08)/year for NT ( $p=.002$ ), an increase of 40%.

Discussion: Using individual longitudinal analyses, accelerated amyloid accumulation in DS is observed, This has important considerations for informing treatment trial design and monitoring beta-amyloid changes in future AD studies involving individuals with DS.

Highlights: Aβ accumulation rate was estimated using a logistic growth model. There was no overlap in the age of amyloid positivity between DS and NT cohorts. Participants with DS accumulate amyloid 40% faster than those with sporadic AD.

Keywords: Alzheimer's disease; PET imaging; Trisomy 21; [C‐11]PiB; amyloid beta (Aβ) plaques; longitudinal.