Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology

Amyloid beta (A beta) peptides generated from the amyloid precursor protein (APP) play a critical role in the development of Alzheimer's disease (AD) pathology. A beta-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 A beta(1-40) 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 A beta production or by neutralizing exosomal A beta peptide with an anti-A beta antibody. These results, taken together, suggest that exosomes derived from cholesterol-accumulated astrocytes can play an important role in trafficking APP/A beta peptides and influencing neuronal viability in the affected regions of the AD brain.

Automated summary

The study found that exosomes derived from cholesterol-accumulated astrocytes contain higher levels of A beta peptide, indicating their importance in AD pathology. In addition, exosomes may also lead to neurodegeneration, which can be attenuated by decreasing A beta production or using anti-A beta antibody.