Comparison of longitudinal Aβ in nondemented elderly and Down syndrome

Neurobiol Aging. 2019 Jan;73:171-176. doi: 10.1016/j.neurobiolaging.2018.09.030. Epub 2018 Sep 27.

Abstract

Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([11C]PiB), a pattern of striatal amyloid beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [11C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented elderly (NDE) population. The purpose of this work was to assess longitudinal changes in trajectories of Aβ in a nondemented DS compared to an NDE cohort. The regional trajectories for anterior ventral striatum (AVS), frontal cortex, and precuneus [11C]PiB retention were explored over time using linear mixed effects models with fixed effects of time, cohort, and time-by-cohort interactions and subject as random effects. Significant differences between DS and NDE cohort trajectories for all 3 region of interests were observed (p < 0.05), with the DS cohort showing a faster accumulation in the AVS and slower accumulation in the frontal cortex and precuneus compared to the NDE cohort. These data add to the previously reported distinct pattern of early striatal deposition not commonly seen in sporadic AD by demonstrating that individuals with DS may also accumulate Aβ at a rate faster in the AVS when compared to NDE subjects.

Keywords: Alzheimer's disease; Amyloid; Down syndrome.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Cohort Studies
  • Down Syndrome / metabolism*
  • Female
  • Frontal Lobe / metabolism*
  • Heterozygote
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Parietal Lobe / metabolism*
  • Thiazoles
  • Time Factors
  • Ventral Striatum / metabolism*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Thiazoles