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 beta (A beta) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD. Methods: AD neuropathogenic proteins A beta(1-42), 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 A beta(1-42), 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 A beta(1-42), P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available. (C) 2016 Published by Elsevier Inc. on behalf of the Alzheimer's Association.