Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome

Eric D Hamlett; Edward J Goetzl; Aurélie Ledreux; Vitaly Vasilevko; Heather A Boger; Angela LaRosa; David Clark; Steven L Carroll; María Carmona-Iragui; Juan Fortea; Elliott J Mufson; Marwan Sabbagh; Abdul H Mohammed; Dean Hartley; Eric Doran; Ira T Lott; Ann-Charlotte Granholm

doi:10.1016/j.jalz.2016.08.012

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.

Authors

Eric D Hamlett¹, Edward J Goetzl², Aurélie Ledreux¹, Vitaly Vasilevko³, Heather A Boger⁴, Angela LaRosa⁵, David Clark⁶, Steven L Carroll⁷, María Carmona-Iragui⁸, Juan Fortea⁸, Elliott J Mufson⁹, Marwan Sabbagh⁹, Abdul H Mohammed¹⁰, Dean Hartley¹¹, Eric Doran¹², Ira T Lott¹², Ann-Charlotte Granholm¹³

Affiliations

¹ Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; The Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA.
² Geriatric Research Center of the Jewish Home of San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.
³ University of California, Irvine Institute for Memory Impairment and Neurological Disorders, Irvine, CA, USA.
⁴ 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.
⁵ Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
⁶ Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.
⁷ Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.
⁸ 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.
⁹ Barrow Neurological Institute, Department of Neurobiology, Phoenix, AZ, USA.
¹⁰ Department of Psychology, Linnaeus University, Växjo, Sweden; Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
¹¹ Alzheimer's Association, Chicago, IL, USA.
¹² Department of Pediatrics, School of Medicine, University of California, Irvine, Orange, CA, USA.
¹³ 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: [email protected].

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 Aβ_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 Aβ_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 Aβ_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.

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

Abstract

MeSH terms

Substances

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