Brain cell-derived exosomes in plasma serve as neurodegeneration biomarkers in male cynomolgus monkeys self-administrating oxycodone

Exosomes in Age-Related Cognitive Decline: Mechanistic Insights and Improving Outcomes

“…Thus, exosomes released by neurons, astrocytes, oligodendrocytes, microglia, endothelial cells and pericytes can be differentiated according to antibody-based purification utilizing L1CAM (L1 cell adhesion molecule), GLAST (Glutamate aspartate transporter), PLP1 (Proteolipid protein 1), TMEM119 (Transmembrane protein 119), CD31 (cluster of differentiation 31) and PDGFRβ (platelet-derived growth factor receptor beta), respectively ( Frühbeis et al, 2020 ; Kumar et al, 2020 ). The capacity to identify a given exosome’s parent cell is particularly valuable given that peripheral exosomes can penetrate the blood-brain-barrier (BBB), while brain derived exosomes can be readily detected in systemic samples ( Alvarez-Erviti et al, 2011 ; Banks et al, 2020 ; Kumar et al, 2021 ). It should be noted that a recent investigation suggested L1CAM may not be an appropriate marker to identify neuronal specific exosomes ( Norman et al, 2021 ); however, the interpretation of such data as well as the reliability of these findings remain contested, including contrary evidence of L1CAM positive vesicles enriched for neuronal proteins (e.g., BDNF, neuronal enolase) ( Mustapic et al, 2017 ; Suire et al, 2017 ).…”

Extracellular Vesicles Taken up by Astrocytes

“…Recently, however, it has become clear that EVs are also secreted in the healthy brain. For example, it has been shown that EVs derived from brain cells exist in the peripheral blood of cynomolgus monkeys [ 20 ]. Furthermore, EVs are reported to be secreted by almost all major brain cells, including neurons [ 7 ], astrocytes [ 10 ], oligodendrocytes [ 21 ], and microglia [ 22 ].…”

‘Treasure’ in garbage bags: extracellular vesicles based biomarker for neurological diseases

“…Analyzing the cargos of EVs seems more reasonable as those could possibly reflect the pathophysiological state of the parent cells. Many studies have shown that analyzing the EV cargos (mainly proteins and miRNAs) can predict the onset, progression, and treatment response of psychological disorders (13,15,21). The pathological proteins associated with neurodegenerative diseases like α-synuclein, p-tau/ tau, and amyloid β could be transported through EVs to nonpathological areas promoting the progression of disease (22,23).…”

“…Ledreux et al reported that the NDEVs isolated from the individuals with Down syndrome and AD are loaded with p-Tau and have the tau seeding capacity to spread tau pathology in the mouse brain (14). Recently, our group also reported the utility of NDEVs and other brain cell-derived EVs in identifying the neurodegenerative and pro-inflammatory effects of oxycodone self-administration in cynomolgus monkeys (15).…”