The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B

Abstract

Introduction: In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology.

Methods: PET imaging with carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellar gray matter as the reference region.

Results: Multiple linear regression revealed slight but highly significant (corrected P < .05) positive correlations between SUVR and age. The striatum showed the strongest correlation, followed by precuneus, parietal cortex, anterior cingulate, frontal cortex, and temporal cortex.

Conclusion: There is an age-related amyloid-β deposition in the DS population, but as a pattern of elevated cortical retention becomes apparent, the correlation of SUVR with age ceases to be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.

Keywords: Aging; Alzheimer's disease; Amyloid imaging; Down syndrome; PiB.

Figure 1

Patterns of [¹¹C]PiB retention. Representative subjects showing the three general patterns of [¹¹C]PiB SUVR in a common slice (52,71,43): nonspecific white matter uptake (top row), elevated striatal uptake only (middle row), and elevated striatal and cortical uptake (bottom row). Arrows in the middle row denote the striatum.

Figure 2

Parametric t-map of the correlation between SUVR and age in the striatum for the whole cohort. Close inspection of the internal structures of the striatum reveals the putamen has higher t-statistics than the caudate (P<0.001), indicating a statistically stronger correlation between standard uptake value ratios and age. This should not be confused with Pearson correlation coefficients, which reflect the strength of the correlations.

Figure 3

Prevalence of PiB positivity by region of interest and age group. A) The percent of PiB positive subjects generally increases with age. Note that this represents the prevalence of participants being classified as PiB positive per age group and does not represent amyloid deposition or amyloid deposition rates. B) The prevalence of PiB positivity of the striatal components with the value of the whole striatum represented as the black line.

Figure 4

Mean SUVRs versus age for each ROI. Mean SUVRs plotted against age (30-53 years) for PiB positive subjects (triangles) and PiB negative subjects (circles). Filled shapes are APOE4 positive. The cutoff value for each ROI was determined by sparse k-means clustering and is represented by the bar.