Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology.
Dis Model Mech
; 14(10)2021 10 01.
Article
em En
| MEDLINE
| ID: mdl-34524402
ABSTRACT
Amyloid ß (Aß) peptides generated from the amyloid precursor protein (APP) play a critical role in the development of Alzheimer's disease (AD) pathology. Aß-containing neuronal exosomes, which represent a novel form of intercellular communication, have been shown to influence the function/vulnerability of neurons in AD. Unlike neurons, the significance of exosomes derived from astrocytes remains unclear. In this study, we evaluated the significance of exosomes derived from U18666A-induced cholesterol-accumulated astrocytes in the development of AD pathology. Our results show that cholesterol accumulation decreases exosome secretion, whereas lowering cholesterol increases exosome secretion, from cultured astrocytes. Interestingly, exosomes secreted from U18666A-treated astrocytes contain higher levels of APP, APP-C-terminal fragments, soluble APP, APP secretases and Aß1-40 than exosomes secreted from control astrocytes. Furthermore, we show that exosomes derived from U18666A-treated astrocytes can lead to neurodegeneration, which is attenuated by decreasing Aß production or by neutralizing exosomal Aß peptide with an anti-Aß antibody. These results, taken together, suggest that exosomes derived from cholesterol-accumulated astrocytes can play an important role in trafficking APP/Aß peptides and influencing neuronal viability in the affected regions of the AD brain.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Astrócitos
/
Colesterol
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Exossomos
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Doença de Alzheimer
Limite:
Animals
Idioma:
En
Revista:
Dis Model Mech
Assunto da revista:
MEDICINA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá