Title

Neuronal Exosomes Reveal Alzheimer's Disease Biomarkers in Down syndrome

Authors

Eric D. Hamlett, Department of Neuroscience, Medical University of South Carolina, The Knoebel Institute for Healthy Aging, University of Denver
Edward J. Goetzl, Geriatric Research Center of the Jewish Home of San Francisco, Department of Medicine, University of California
Aurélie Ledreux, Department of Biological Sciences and the Knoebel Institute for Healthy Aging, University of Denver, Department of Neuroscience, Medical University of South CarolinaFollow
Vitaly Vasilevko, University of California, Irvine Institute for Memory Impairment and Neurological Disorders
Heather A. Boger, Department of Neuroscience, Medical University of South Carolina, The Center on Aging, Department of Neuroscience, Medical University of South Carolina
Angela LaRosa, Department of Pediatrics, Medical University of South Carolina
David Clark, Department of Neurology, Medical University of South Carolina
Steven L. Carroll, Department of Pathology and Laboratory Medicine, Medical University of South Carolina
María Carmona-Iragui, Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, Down Medical Center, Fundacío Catalana Síndrome de Down
Juan Fortea, Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, Down Medical Center, Fundacío Catalana Síndrome de Down
Elliott J. Mufson, Barrow Neurological Institute, Department of Neurobiology
Marwan Sabbagh, Barrow Neurological Institute, Department of Neurobiology
Abdul H. Mohammed, Department of Psychology, Linnaeus University, Center for Alzheimer Research, Karolinska Institutet
Dean Hartley, Alzheimer's Association
Eric Doran, Department of Pediatrics, School of Medicine, University of California
Ira T. Lott, Department of Pediatrics, School of Medicine, University of California
Ann‐Charlotte Granholm, Department of Biological Sciences and the Knoebel Institute for Healthy Aging, University of DenverFollow

Document Type

Article

Publication Date

10-15-2016

Keywords

Intellectual disability, Down syndrome, Alzheimer's disease, Blood biomarkers, Neuronal exosomes, Hyperphosphorylated tau, Amyloid-β

Organizational Units

Knoebel Institute for Healthy Aging

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.

Publication Statement

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