Abstract
Exosomes, a type of extracellular vesicle, have been shown to be involved in many disorders, including Alzheimer’s disease (AD). Exosomes may contribute to the spread of misfolded proteins such as amyloid-β (Aβ) and α-synuclein. However, the specific diffusion process of exosomes and their final destination in brain are still unclear. In the present study, we isolated exosomes from peripheral plasma and injected them into the hippocampus of an AD mouse model, and investigated exosome diffusion. We found that injected exosomes can spread from the dentate gyrus (DG) to other regions of hippocampus and to the cortex. Exosomes targeted microglia preferentially; this phenomenon is stable and is not affected by age. In AD mice, microglia take up lower levels of exosomes. More interestingly, plasma exosomes cluster around the Aβ plaques and are engulfed by activated microglia nearby. Our data indicate that exosomes can diffuse throughout the brain and may play a role in the dynamics of amyloid deposition in AD through microglia.
Highlights
Exosomes are a bioactive vesicle (40–100 nm) secreted by various cells in vitro and in vivo under physiological and pathological conditions
Previous studies have demonstrated that exosomes facilitate the unique transmissible nature of prions (Vella et al, 2007; Guo et al, 2016)
Many proteins associated with Alzheimer’s disease (AD) including Aβ precursor protein (APP) and the APP-processing products, C-terminal fragments and Aβ can be found in exosomes from both neuronal cell cultures and brain tissues (Rajendran et al, 2006; Vingtdeux et al, 2007; Perez-Gonzalez et al, 2012)
Summary
Exosomes are a bioactive vesicle (40–100 nm) secreted by various cells in vitro and in vivo under physiological and pathological conditions. A number of proteins related to neurodegenerative disorders, including prion disease, Parkinson’s disease and Alzheimer’s disease (AD), have been shown to be released by cells in association with exosomes (Coleman and Hill, 2015). Exosomes have been suspected to participate in the prion-like propagation of lesions in AD (Bellingham et al, 2012; Vingtdeux et al, 2012; Coleman and Hill, 2015) This idea is supported by the observation that exosomes isolated from either neuronal cell cultures or brain contain Aβ precursor protein (APP) and APP-processing products, including C-terminal fragments and Aβ (Vingtdeux et al, 2007; Perez-Gonzalez et al, 2012). We investigated the role of exosomes in amyloid deposition in an AD transgenic mouse model
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