Altered levels of plasma neuron‐derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury

What is it about?

Small cell-derived particles called exosomes are in plasma and can be isolated by antibodies to protein markers on the cells of origin of the exosomes. Neuron-derived exosomes (NDEs) were enriched by anti-L1CAM antibody absorption from plasmas of subjects ages 18-26 years within one week after a sports-related mild traumatic brain injury (acute mTBI) (n=18), three months or longer after the last of two to four mTBIs (chronic mTBI) (n=14) and with no recent history of TBI (controls) (n=21). Plasma concentrations of NDEs, assessed by counts and levels of the exosome marker CD81, were significantly depressed by a mean of 45% in acute mTBI (P<0.0001), but not chronic mTBI, compared to controls. In acute, but not chronic mTBI, mean CD81-normalized NDE levels of a range of brain-expressed functional neural proteins were significantly abnormal relative to those of controls, including those involved in exosome traffic in cells, neuron structure, neuron movement of water and ions, and blood-brain barrier permeability. In chronic mTBI, there were significantly elevated mean CD81-normalized NDE levels of Aβ42,P-T181-tau,P-S396-tau,IL-6 and PRPc,that are implicated in neurodegeneration, with a greater (IL-6 and PRPc),lesser or no (P-S396-tau) significant increase in acute mTBI. Abnormalities in NDE levels of neuro-functional proteins in acute mTBI, but not chronic mTBI, and greater elevations of some neuropathological proteins of NDEs in chronic mTBI than acute mTBI delineate phase-specific mechanisms. Longitudinal studies of more mTBI subjects will be required to establish biomarkers predictive of and possibly etiologically involved in development of neurodegeneration.

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