The gradual deterioration of cognitive functions in Alzheimer's disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligomers of amyloid-beta may cause propagation of pathology in a prion-like manner, although the underlying mechanisms are incompletely understood. Here we show that small extracellular vesicles, exosomes, from Alzheimer patients' brains contain increased levels of amyloid-beta oligomers and can act as vehicles for the neuron-to-neuron transfer of such toxic species in recipient neurons in culture. Moreover, blocking the formation, secretion or uptake of exosomes was found to reduce both the spread of oligomers and the related toxicity. Taken together, our results imply that exosomes are centrally involved in Alzheimer's disease and that they could serve as targets for development of new diagnostic and therapeutic principles.
Journal article
2018-07-01T00:00:00+00:00
136
41 - 56
15
Alzheimer’s disease, Beta-amyloid, Exosomes, Human, Oligomers, Prion-like, Propagation, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Brain, Cell Line, Transformed, Coculture Techniques, Culture Media, Conditioned, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Exosomes, Female, Gene Expression Regulation, Humans, L-Lactate Dehydrogenase, Male, Membrane Proteins, Microscopy, Electron, Transmission, Middle Aged, Neuroblastoma, Organic Chemicals, Peptide Fragments, Pluripotent Stem Cells, Protein Transport, Transcription Factors, Tsg101 Protein