Early striatal amyloid signal in Down Syndrome: Comparison of PiB and Florbetapir PET

Abstract

AbstractBackgroundPET amyloid [11C]PiB imaging has revealed early detection of Ab in the striatum in individuals with Down Syndrome (DS), a group carrying genetic risk for AD. The goal of this investigation is to examine striatal binding of [11C]PiB and [18F]florbetapir (FBP) to determine if similar striatal uptake profiles are observed in individuals with DS.MethodsPET scans were acquired as part of the Alzheimer’s Biomarker Consortium – Down Syndrome (ABC‐DS) study. DS participants were scanned with either PiB (n=204; ages 25‐56 yrs) or FBP (n=84; ages 40‐85 yrs) at seven academic sites. SUVR images were created with acquisition times of 50‐70min for both radiotracers, using a cerebellar reference region. ROIs were defined for the anterior ventral striatum (AVS) and the full cortex (CTX). SUVR was then converted to centiloids (CL) using published methods (Klunk 2015) with DS‐specific modifications, including AVS extraction and approximate CL_AVS. Aβ(+) was defined using a threshold of 18.1 CL in CTX ROI, categorizing Aβ(‐) and Aβ(+) groups. Comparisons across PiB and FBP examined 1) the proportion of CL_AVS values exceeding the threshold in the Aβ(‐) group and 2) the difference between SUVR_AVS and SUVR_CTX in the Aβ(+) group.Results58/204 subjects (PiB) and 72/84 subjects (FBP) were Aβ(+), with differences in Aβ(+) presumably due to greater age and advanced neurodegeneration in the FBP group. For the Aβ(‐) comparison, elevated CL_AVS was detected in 16/146 (PiB) and 0/12 (FBP). The average CL_AVS of those that exceeded the threshold was 37.0±12.7 CL (PiB) (mean±SD). For the Aβ(+) comparison, 52/58 (PiB) and 52/72 (FBP) had CL_AVS greater than their CL_CTX. The average difference between SUVR_AVS and SUVR_CTX for the Aβ(+) group was 0.50±0.39 SUVR (46.9±36.8 CL) (PiB) and 0.08±0.18 SUVR (14.2±31.0 CL) (FBP).ConclusionsPiB PET exhibited higher uptake in the striatum during early stages of amyloid deposition. PiB revealed a 6x greater difference than FBP between striatal to cortical SUVR in the Aβ(+) group. Neuropathological investigation is ongoing to characterize these differences in striatal binding in DS. Despite this difference in early‐stage binding, both PiB and FBP demonstrate sensitivity for determining the presence of Aβ in DS.