Abstract
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Background: Adults with Down syndrome (DS) carry a triplicate copy of chromosome 21 resulting in the overproduction of amyloid precursor protein, with earliest deposition of Aβ plaques predominantly in the striatum. The relationship between amyloid overproduction and neurodegeneration in DS is not yet understood but will be valuable to compare against the observed patterns in late-onset Alzheimer’s disease (AD).
Objectives: The goal of this study is to relate PiB measured Aβ deposition to regional glucose metabolism during the progression of AD in DS, with a focus on the striatum to identify how the prominence and duration of Aβ in this region influences neurodegeneration.
Methods: A subgroup of 81 adults with DS (age = 38.9 ± 8.3 years) from the ongoing Alzheimer’s Biomarker Consortium-Down Syndrome study (ABC-DS) underwent [F-18]FDG PET in addition to [C-11]PiB. 50-70 minute PiB SUVr and 40-60 minute FDG SUVr images were created using cerebellar gray matter as a reference region. The images were spatially normalized to MNI152 space using DS-specific PET templates for PiB and FDG. Voxel-based regressions were performed between the PiB and FDG images using the Biological Parametric Mapping toolbox in SPM8. The resulting T-statistic maps were evaluated at an uncorrected height threshold of P = 0.001. Additionally, an ROI-based analysis was performed between PiB and FDG SUVr in the caudate and putamen using Pearson’s correlations.
Results: The voxel-based analysis revealed significant negative associations between PiB and FDG in the cingulate, temporal cortex, parietal cortex and precuneus (Figure 1). The regional analysis showed no significant association between PiB and FDG in the caudate (Pearson’s R[95% CI’s] = -0.07[-0.28, 0.15], P = 0.53) or putamen (Pearson’s R = 0.00[-0.21, 0.21], P = 0.99) (Figure 2). Discussion: These results reveal patterns of regional hypometabolism during AD progression in DS. Significant negative associations between PiB and FDG in DS (notably in the temporal cortex, parietal cortex and precuneus) are similar to that observed in late-onset AD (including the lack of association in frontal cortex). Although the caudate and putamen are the earliest regions showing PiB-binding (and so of deposition of Aβ), no significant reductions in metabolism are evident, suggesting the localization of Aβ in these regions may not lead to neurodegeneration as measured with FDG.
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