Longitudinal PET imaging identifies earliest stages of Aβ accumulation in Down syndrome

Abstract

AbstractBackgroundAdults with Down syndrome (DS) are genetically predisposed to Alzheimer’s disease (AD) and accumulate beta‐amyloid plaques (Aβ) early in life. Our previous work in this population comparing centiloids and amyloid load (AβL) identified an amyloid‐positive cutoff of 20 AβL. The aim of this study was to evaluate longitudinal AβL change across DS groups based on Aβ status.Method175 adults with DS (age=39.8 (8.64) years) were recruited through the Alzheimer’s Biomarker Consortium ‐ Down Syndrome study. Of the 175 adults, N=79 underwent up to four longitudinal [C‐11]PiB scans (2.64 (0.71) years apart). Longitudinal Aβ change was calculated for each individual using AβL. Cluster analysis identified a group of A‐ individuals with significant Aβ increase at subthreshold detection levels, and was used to inform a subthreshold A+ cutoff. Rates of AβL change were compared across groups of A‐ (AβL < 13.3), subthreshold A+ (13.3 < AβL < 20) and A+ (AβL > 20) DS. Average SUVr images were then generated across all participants for each group and SUVrs were extracted to evaluate regional Aβ burden.ResultThe A‐ group showed longitudinal change of 0.32 (0.66) AβL/year, while the subthreshold A+ and A+ groups showed change of 2.60 (1.11) and 3.22 (1.26) AβL/year, respectively (Figure 1). AβL change was statistically different across all groups (ANCOVA F = 76.7, p < .0001) while adjusting for imaging site. Post hoc Student’s t‐tests revealed that the subthreshold A+ and A+ groups had significantly greater AβL change compared to the A‐ group (Bonferroni‐adjusted p < .0001). No significant difference in AβL change was observed between the subthreshold A+ and A+ groups. Figure 2 displays the average SUVr images for each Aβ group. Relative to the A‐ group, the subthreshold A+ group showed greater regional Aβ burden (Table 1).ConclusionDS adults with a subthreshold A+ classification showed indistinguishable rates of Aβ change compared to those who are conventionally A+, suggesting that longitudinal PET imaging can identify significant Aβ change early during AD progression. These longitudinal findings can inform sample size estimates for AD clinical trials aimed at early intervention in this population.