title: Plasma Exosomes Spread and Cluster Around β-Amyloid Plaques in an Animal Model of Alzheimer's Disease.
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.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Zhangyu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine Hangzhou, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine Hangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine Hangzhou, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine Hangzhou, China.
authors.forename: Binggui
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Baorong
authors.initials: B
authors.lastname: Zhang
keywords: Alzheimer’s disease; aging; exosomes; microglia; β-amyloid plaques