Jul 20, 2014

Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice

The Journal of Biological Chemistry
Kohei YuyamaYasuyuki Igarashi


Elevated levels of amyloid-β peptide (Aβ) in the human brain are linked to the pathogenesis of Alzheimer disease. Recent in vitro studies have demonstrated that extracellular Aβ can bind to exosomes, which are cell-secreted nanovesicles with lipid membranes that are known to transport their cargos intercellularly. Such findings suggest that the exosomes are involved in Aβ metabolism in brain. Here, we found that neuroblastoma-derived exosomes exogenously injected into mouse brains trapped Aβ and with the associated Aβ were internalized into brain-resident phagocyte microglia. Accordingly, continuous intracerebral administration of the exosomes into amyloid-β precursor protein transgenic mice resulted in marked reductions in Aβ levels, amyloid depositions, and Aβ-mediated synaptotoxicity in the hippocampus. In addition, we determined that glycosphingolipids (GSLs), a group of membrane glycolipids, are highly abundant in the exosomes, and the enriched glycans of the GSLs are essential for Aβ binding and assembly on the exosomes both in vitro and in vivo. Our data demonstrate that intracerebrally administered exosomes can act as potent scavengers for Aβ by carrying it on the exosome surface GSLs and suggest a role of exosomes in A...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Pathogenic Aspects
Tissue Membrane
Central Neuroblastoma
APP protein, human

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques. Here is the latest research.

Alzheimer's Disease: Animal models

Alzheimer's disease is a chronic neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Alzheimer's Disease: Endosomes

The feed focuses on the role of dysfunctional endosomal trafficking in Alzheimer’s Disease and the potential for targeting the endosome as a therapeutic target.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Alzheimer's Disease: Genes&Microglia

Genes and microglia are associated with the risk of developing and the progression of conditions such as Alzheimer's Disease (AD). Here are the latest discoveries pertaining to this disease.

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.