Neuronal Exosomes Reveal Alzheimer's Disease Biomarkers in Down Syndrome

Authors

Eric D. Hamlett, Medical University of South Carolina, University of Denver
Edward J. Goetzl, Geriatric Research Center of the Jewish Home of San Francisco, University of California
Aurélie Ledreux, University of Denver, Medical University of South CarolinaFollow
Vitaly Vasilevko, University of California
Heather A. Boger, Medical University of South Carolina
Angela LaRosa, Medical University of South Carolina
David Clark, Medical University of South Carolina
Steven L. Carroll, Medical University of South Carolina
María Carmona-Iragui, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, Fundacío Catalana Síndrome de Down
Juan Fortea, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, undacío Catalana Síndrome de Down
Elliott J. Mufson, Barrow Neurological Institute
Marwan Sabbagh, Barrow Neurological Institute
Abdul H. Mohammed, Linnaeus University, Karolinska Institutet
Dean Hartley, Alzheimer's Association
Eric Doran, University of California
Ira T. Lott, University of California
Ann‐Charlotte Granholm, University of DenverFollow

Publication Date

10-15-2016

Document Type

Article

Organizational Units

Knoebel Institute for Healthy Aging

Keywords

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

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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Recommended Citation

Hamlett, Eric D, Goetzl, Edward J, Ledreux, Aurélie, Vasilevko, Vitaly, Boger, Heather A, LaRosa, Angela, . . . Granholm, Ann-Charlotte. (2017). Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome. Alzheimer's & Dementia, 13(5), 541-549. doi: 10.1016/j.jalz.2016.08.012.