The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis

Neurobiol Aging. 2017 May:53:11-19. doi: 10.1016/j.neurobiolaging.2017.01.009. Epub 2017 Jan 17.

Abstract

People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging-the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.

Keywords: Alzheimer's disease; Amyloid; Cortical thickness; Down syndrome; Gray matter volume.

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloidosis / diagnostic imaging
  • Amyloidosis / pathology*
  • Aniline Compounds
  • Brain Diseases, Metabolic / diagnostic imaging
  • Brain Diseases, Metabolic / pathology*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology*
  • Cross-Sectional Studies
  • Down Syndrome / diagnostic imaging
  • Down Syndrome / pathology*
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Thiazoles

Substances

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