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. 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: Lotta.granholm-bentley@DU.edu.
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.
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.
Authors: Nicole Schupf; Annie Lee; Naeun Park; Lam-Ha Dang; Deborah Pang; Alexander Yale; David Kyung-Taek Oh; Sharon J Krinsky-McHale; Edmund C Jenkins; José A Luchsinger; Warren B Zigman; Wayne Silverman; Benjamin Tycko; Sergey Kisselev; Lorraine Clark; Joseph H Lee Journal: Neurobiol Aging Date: 2015-06-19 Impact factor: 4.673
Authors: Sylvia E Perez; Jennifer C Miguel; Bin He; Michael Malek-Ahmadi; Eric E Abrahamson; Milos D Ikonomovic; Ira Lott; Eric Doran; Melissa J Alldred; Stephen D Ginsberg; Elliott J Mufson Journal: Acta Neuropathol Date: 2019-02-07 Impact factor: 17.088
Authors: Piotr Lewczuk; Peter Riederer; Sid E O'Bryant; Marcel M Verbeek; Bruno Dubois; Pieter Jelle Visser; Kurt A Jellinger; Sebastiaan Engelborghs; Alfredo Ramirez; Lucilla Parnetti; Clifford R Jack; Charlotte E Teunissen; Harald Hampel; Alberto Lleó; Frank Jessen; Lidia Glodzik; Mony J de Leon; Anne M Fagan; José Luis Molinuevo; Willemijn J Jansen; Bengt Winblad; Leslie M Shaw; Ulf Andreasson; Markus Otto; Brit Mollenhauer; Jens Wiltfang; Martin R Turner; Inga Zerr; Ron Handels; Alexander G Thompson; Gunilla Johansson; Natalia Ermann; John Q Trojanowski; Ilker Karaca; Holger Wagner; Patrick Oeckl; Linda van Waalwijk van Doorn; Maria Bjerke; Dimitrios Kapogiannis; H Bea Kuiperij; Lucia Farotti; Yi Li; Brian A Gordon; Stéphane Epelbaum; Stephanie J B Vos; Catharina J M Klijn; William E Van Nostrand; Carolina Minguillon; Matthias Schmitz; Carla Gallo; Andrea Lopez Mato; Florence Thibaut; Simone Lista; Daniel Alcolea; Henrik Zetterberg; Kaj Blennow; Johannes Kornhuber Journal: World J Biol Psychiatry Date: 2017-10-27 Impact factor: 4.132