Brain Derived Exosomes Are a Double-Edged Sword in Alzheimer's Disease.

Zhiqi Song,Yunlin Han,Yanfeng Xu,Pin Yu,Chuan Qin,Hua Zhu,Wenjie Zhao,Yajin Qu,Ling Zhang,Wei Deng

doi:10.3389/fnmol.2020.00079

Abstract

Brain derived exosomes (BDEs) are extracellular nanovesicles that are collectively released by all cell lineages of the central nervous system and contain cargo from their original cells. They are emerging as key mediators of communication and waste management among neurons, glial cells and connective tissue during both physiological and pathological conditions in the brain. We review the rapidly growing frontier of BDEs biology in recent years including the involvement of exosomes in neuronal development, maintenance and communication through their multiple signaling functions. Particularly, we highlight the important role of exosomes in Alzheimer’s disease (AD), both as a pathogenic agent and as a disease biomarker. Our understanding of such unique nanovesicles may offer not only answers about the (patho) physiological course in AD and associated neurodegenerative diseases but also ideal methods to develop these vesicles as vehicles for drug delivery or as tools to monitor brain diseases in a non-invasive manner because crossing the blood brain barrier is an inherent capability of exosomes. BDEs have potential as biomarkers and as therapeutic tools for AD and related brain disorders in the near future.

Highlights

Exosomes are small extracellular nano-sized vesicles between 30 and 150 nm in diameter (DeLeo and Ikezu, 2018) that were first described in the 1980s (Johnstone et al, 1987)
Compared with Alzheimer’s disease (AD) patients who had only been diagnosed with mild cognitive impairment, p-T181-tau levels were significantly higher in brain derived exosomes (BDEs) isolated from the plasma of later-stage AD patients (Winston et al, 2016), demonstrating either a dysfunction of the clearance ability or an increase in pathogenicity of exosomes in later disease states of AD. p-T181and p-S396-tau were significantly decreased in BDEs of patients 1–10 years prior to their AD diagnosis (Fiandaca et al, 2015)
This study demonstrated that significant differences in the insulin receptor substrate 1 (IRS1) levels were recognizable up to 10 years prior to clinical onset of AD, which suggests that proteins within BDEs that are involved in insulin disruption may potentially be useful biomarkers for clinical diagnosis

Summary

Introduction

Exosomes are small extracellular nano-sized vesicles between 30 and 150 nm in diameter (DeLeo and Ikezu, 2018) that were first described in the 1980s (Johnstone et al, 1987). After release into the extracellular space, exosomes can be internalized by recipient cells mediated by the interaction of various exosomal surface proteins and cellular receptors via several mechanisms including phagocytosis, plasma membrane fusion, macropinocytosis and endocytosis (McKelvey et al, 2015).

Results

Conclusion