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: Kohei Yuyama, Hui Sun, Seigo Usuki, Shota Sakai, Hisatoshi Hanamatsu, Tetsuo Mioka, Nobuyuki Kimura, Megumi Okada, Hidetoshi Tahara, Jun-ichi Furukawa, Naoki Fujitani, Yasuro Shinohara, Yasuyuki Igarashi
• Journal: FEBS letters (FEBS Lett) Vol. 589 Issue 1 Pg. 84-8 (Jan 02 2015) ISSN: 1873-3468 [Electronic] England
• PMID: 25436414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides

Topics

• Alzheimer Disease (cerebrospinal fluid, genetics, pathology)
• Amyloid beta-Peptides (cerebrospinal fluid, genetics)
• Animals
• Exosomes (genetics, metabolism, pathology)
• Humans
• Macaca fascicularis
• Mice
• Mice, Transgenic
• Neuroglia (metabolism, pathology)
• Neurons (metabolism, pathology)