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. 2020 Apr 16;12(1):e12020.
doi: 10.1002/dad2.12020. eCollection 2020.

Amyloid accumulation in Down syndrome measured with amyloid load

Matthew D Zammit  1 , Charles M Laymon  2 , Tobey J Betthauser  3 , Karly A Cody  3 , Dana L Tudorascu  4 , Davneet S Minhas  2 , Marwan N Sabbagh  5 , Sterling C Johnson  3 , Shahid H Zaman  6 , Chester A Mathis  2 , William E Klunk  7 , Benjamin L Handen  7 , Ann D Cohen  7 , Bradley T Christian  1
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Free PMC article

Amyloid accumulation in Down syndrome measured with amyloid load

Matthew D Zammit et al. Alzheimers Dement (Amst). .
Free PMC article

Abstract

Introduction: Individuals with Down syndrome (DS) show enhanced amyloid beta (Aβ) deposition in the brain. A new positron emission tomography (PET) index of amyloid load (AβL ) was recently developed as an alternative to standardized uptake value ratios (SUVrs) to quantify Aβ burden with high sensitivity for detecting and tracking Aβ change.1.

Methods: AβL was calculated in a DS cohort (N = 169, mean age ± SD = 39.6 ± 8.7 years) using [C-11]Pittsburgh compound B (PiB) PET imaging. DS-specific PiB templates were created for Aβ carrying capacity (K) and non-specific binding (NS).

Results: The highest values of Aβ carrying capacity were found in the striatum and precuneus. Longitudinal changes in AβL displayed less variability when compared to SUVrs.

Discussion: These results highlight the utility of AβL for characterizing Aβ deposition in DS. Rates of Aβ accumulation in DS were found to be similar to that observed in late-onset Alzheimer's disease (AD; ≈3% to 4% per year), suggesting that AD progression in DS is of earlier onset but not accelerated.

Keywords: Alzheimer's disease; Down syndrome; PiB; amyloid PET; amyloid load; longitudinal.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Longitudinal rate of PiB change relative to baseline global SUVr fit by a restricted cubic spline (left). Integral of the fit representing AD chronology with respect to global SUVr (right)
FIGURE 2
FIGURE 2
DS‐specific parametric images for carrying capacity (K) and non‐specific binding (NS) displayed as orthographic planes with corresponding gray and white matter maps
FIGURE 3
FIGURE 3
Comparison of AβL and non‐specific uptake (ns) to Global PiB SUVr. Participants were classified as Aβ(+) if their AβL exceeded the cutoff of 20.0%
FIGURE 4
FIGURE 4
Dependence of AβL on age at the time of scan. Empty circles represent participants that have completed just one cycle of PiB imaging. The dashed line represents the cutoff for Aβ(+)
FIGURE 5
FIGURE 5
Distribution of longitudinal change in AβL and global PiB SUVr. Lower longitudinal variability is observed for AβL compared to SUVr for both Aβ(−) and Aβ(+) cases
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