The pattern of amyloid accumulation in the brains of adults with Down syndrome

Alzheimers Dement. 2016 May;12(5):538-45. doi: 10.1016/j.jalz.2015.07.490. Epub 2015 Sep 9.

Abstract

Introduction: Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis.

Methods: Forty-nine adults with DS aged 25-65 underwent positron emission tomography with Pittsburgh compound-B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status.

Results: Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function.

Discussion: PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.

Keywords: Alzheimer's disease; Amyloid; Dementia; Down syndrome; PET; PIB; Preclinical; Striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Alzheimer Disease / epidemiology
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Cerebral Cortex / metabolism*
  • Down Syndrome / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Radiopharmaceuticals