The striatum is an early, accurate indicator of amyloid burden using [¹¹C]PiB in Down syndrome: Comparison of two radiotracers

INTRODUCTION: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [¹¹C]Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging, which has not been replicated with [¹⁸F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures. METHODS: Longitudinal PiB (n = 175 participants) and FBP (n = 92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome (ABC-DS) were used to measure cortical and striatal binding. Generalized temporal models for cortical and striatal amyloid accumulation were created using the sampled iterative local approximation (SILA) method. RESULTS: PiB demonstrated greater striatal-to-cortical ratios than FBP. SILA analysis revealed striatal amyloid burden occurs 3.40 (2.39) years earlier than the cortex in PiB. There was no difference between the cortex and striatum in FBP. DISCUSSION: Among adults with Down syndrome, the striatum consistently accumulates amyloid earlier than the cortex when measured with PiB. This suggests the striatum is more sensitive to the onset of PiB PET-detectable amyloid in Down syndrome. Highlights: Striatal amyloid is detectable 3.4 years before the cortex using PiB PET in DS. Florbetapir PET does not detect early striatal amyloid accumulation in DS. White matter can be used as reference region in longitudinal florbetapir PET. SILA trajectory models can be used to compare regional estimates for age of onset.