title: Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; The Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hamlett
authors.affiliation: Geriatric Research Center of the Jewish Home of San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Goetzl
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; The Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ledreux
authors.affiliation: University of California, Irvine Institute for Memory Impairment and Neurological Disorders, Irvine, CA, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Vasilevko
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; The Center on Aging, Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boger
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: LaRosa
authors.affiliation: Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Clark
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Carroll
authors.affiliation: Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, Barcelona, Spain; Down Medical Center, Fundacío Catalana Síndrome de Down, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Carmona-Iragui
authors.affiliation: Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, Barcelona, Spain; Down Medical Center, Fundacío Catalana Síndrome de Down, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: Barrow Neurological Institute, Department of Neurobiology, Phoenix, AZ, USA.
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.affiliation: Barrow Neurological Institute, Department of Neurobiology, Phoenix, AZ, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Sabbagh
authors.affiliation: Department of Psychology, Linnaeus University, Växjo, Sweden; Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Abdul H
authors.initials: AH
authors.lastname: Mohammed
authors.affiliation: Alzheimer's Association, Chicago, IL, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Hartley
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, Irvine, Orange, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Doran
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, Irvine, Orange, CA, USA.
authors.forename: Ira T
authors.initials: IT
authors.lastname: Lott
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; The Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA; The Center on Aging, Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden. Electronic address: Lotta.granholm-bentley@DU.edu.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Granholm
mesh_terms: D000293:Adolescent; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004314:Down Syndrome / Q000097:blood*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D055815:Young Adult; D016875:tau Proteins / Q000097:blood
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D016875:tau Proteins
keywords: Alzheimer's disease; Amyloid-β; Blood biomarkers; Down syndrome; Hyperphosphorylated tau; Intellectual disability; Neuronal exosomes