title: A potential function for neuronal exosomes: sequestering intracerebral amyloid-β peptide.
abstract: Elevated amyloid-β peptide (Aβ) in brain contributes to Alzheimer's disease (AD) pathogenesis. We demonstrated the presence of exosome-associated Aβ in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated Aβ notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but not glial exosomes, had abundant glycosphingolipids and could capture Aβ. Infusion of neuronal exosomes into brains of APP transgenic mice decreased Aβ and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. These findings highlight the role of neuronal exosomes in Aβ clearance, and suggest that their downregulation might relate to Aβ accumulation and, ultimately, the development of AD pathology.
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan. Electronic address: kyuyama@pharm.hokudai.ac.jp.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yuyama
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Usuki
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Hanamatsu
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan; Division of Molecular Interaction, Institute for Genetic Medicine, Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Mioka
authors.affiliation: Section of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kimura
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furukawa
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujitani
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Shinohara
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D000818:Animals; D055354:Exosomes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides
keywords: APP transgenic mouse; Alzheimer’s disease; Amyloid-β peptide; Cerebrospinal fluid; Cynomolgus monkey; Exosome