Abstract
Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.
Highlights
Extracellular vesicles (EVs) are released from virtually all cell types, including cells in the central nervous system (CNS) such as oligodendrocytes, neurons, astrocytes, microglia and Schwann cells, as well as endothelial cells [1,2]
EVs are comprised of shedding exosomes (40 to 100 nm in diameter), microvesicles and apoptotic bodies, which vary in size, cellular origin, process biogenesis and biophysical properties [7]
Whereas microvesicles are heterogeneous in size, exosomes that originate from multivesicular bodies (MVBs) of the endosomal system are relatively homogeneous in size and density
Summary
Extracellular vesicles (EVs) are released from virtually all cell types, including cells in the central nervous system (CNS) such as oligodendrocytes, neurons, astrocytes, microglia and Schwann cells, as well as endothelial cells [1,2]. EVs are comprised of shedding exosomes (40 to 100 nm in diameter), microvesicles and apoptotic bodies, which vary in size, cellular origin, process biogenesis and biophysical properties [7]. MVBs can fuse with the plasma membrane, leading to the release of the ILVs as exosomes into the extracellular space [15,16]. When MVBs are fused with the plasma membrane, the carrying molecules might act as mediators in biochemical signaling in adjacent or remote recipient cells. It is not yet elucidated how the fate of MVBs are determined. The fusion of MVBs with the plasma membrane is controlled by the soluble NSF-attachment protein receptor complex, which is involved in the conventional calcium-regulated exocytosis of lysosomes [28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
