Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome

Alzheimers Dement. 2017 May;13(5):541-549. doi: 10.1016/j.jalz.2016.08.012. Epub 2016 Oct 15.

Abstract

Introduction: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD.

Methods: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls.

Results: Neuronal exosome levels of Aβ1-42, P-T181-tau, and P-S396-tau were significantly elevated in individuals with DS compared with age-matched controls at all ages beginning in childhood. No significant gender differences were observed.

Discussion: These early increases in Aβ1-42, P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.

Keywords: Alzheimer's disease; Amyloid-β; Blood biomarkers; Down syndrome; Hyperphosphorylated tau; Intellectual disability; Neuronal exosomes.

MeSH terms

  • Adolescent
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / blood
  • Biomarkers / blood
  • Down Syndrome / blood*
  • Exosomes / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Young Adult
  • tau Proteins / blood

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • tau Proteins