Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome
Por:
Hamlett, ED, Goetzl, EJ, Ledreux, A, Vasilevko, V, Boger, HA, LaRosa, A, Clark, D, Carroll, SL, Carmona-Iragui, M, Fortea, J, Mufson, EJ, Sabbagh, M, Mohammed, AH, Hartley, D, Doran, E, Lott, IT, Granholm, AC
Publicada:
1 may 2017
Resumen:
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.
Filiaciones:
Hamlett, ED:
Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA
Univ Denver, Knoebel Inst Hlth Aging, Denver, CO 80208 USA
Goetzl, EJ:
Jewish Home San Francisco, Geriatr Res Ctr, San Francisco, CA USA
Univ Calif San Francisco, Dept Med, San Francisco, CA USA
Ledreux, A:
Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA
Univ Denver, Knoebel Inst Hlth Aging, Denver, CO 80208 USA
Vasilevko, V:
Univ Calif Irvine, Irvine Inst Memory Impairment & Neurol Disorders, Irvine, CA USA
Boger, HA:
Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA
Med Univ South Carolina, Dept Neurosci, Ctr Aging, Charleston, SC 29425 USA
LaRosa, A:
Med Univ South Carolina, Dept Pediat, Charleston, SC USA
Clark, D:
Med Univ South Carolina, Dept Neurol, Charleston, SC USA
Carroll, SL:
Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC USA
Carmona-Iragui, M:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Memory Unit, Neurol Dept, Barcelona, Spain
Fundacio Catalana Sindrome Down, Down Med Ctr, Barcelona, Spain
Fortea, J:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Memory Unit, Neurol Dept, Barcelona, Spain
Fundacio Catalana Sindrome Down, Down Med Ctr, Barcelona, Spain
Mufson, EJ:
Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA
Sabbagh, M:
Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA
Mohammed, AH:
Linnaeus Univ, Dept Psychol, Vaxjo, Sweden
Karolinska Inst, Ctr Alzheimer Res, Huddinge, Sweden
Hartley, D:
Alzheimers Assoc, Chicago, IL USA
Doran, E:
Univ Calif Irvine, Dept Pediat, Sch Med, Orange, CA 92717 USA
Lott, IT:
Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA
Univ Calif Irvine, Dept Pediat, Sch Med, Orange, CA 92717 USA
Granholm, AC:
Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA
Univ Denver, Knoebel Inst Hlth Aging, Denver, CO 80208 USA
Med Univ South Carolina, Dept Neurosci, Ctr Aging, Charleston, SC 29425 USA
Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA
Karolinska Inst, Ctr Alzheimer Res, Huddinge, Sweden
Green Accepted
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