Citation

Goetzl EJ, Ledreux A, Granholm AC, Elahi FM, Goetzl L, Hiramoto J, Kapogiannis D. Front. Neurosci. 2019; 13: e452.

Affiliation

Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD, United States.

Copyright

(Copyright © 2019, Frontiers Research Foundation)

DOI

10.3389/fnins.2019.00452

PMID

31133789

PMCID

PMC6517542

Abstract

The recent recognition that Alzheimer disease-like pathology may be found in chronic traumatic encephalopathy (CTE) even after acute mild traumatic brain injury (mTBI) has increased the urgency of elucidating mechanisms, identifying biomarkers predictive of high risk of development of CTE, and establishing biomarker profiles indicative of impactful effects of treatments. Of the many proteins that are loaded into neuron-derived exosomes (NDEs) from damaged neurons after acute TBI, the levels of prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins remain elevated for months. Prolonged heightened expression of aquaporins and IL-6 may account for the persistent central nervous system edema and inflammation of CTE. PRPc, XIIIa and synaptogyrin-3 bind and concentrate neurotoxic forms of oligomeric amyloid β peptides or P-tau for delivery into neurons at or distant from the site of trauma. Our progression factor hypothesis of CTE asserts that physiological neuronal proteins, such as PRPc, XIIIa, synaptogyrin-3, IL-6 and aquaporins, that increase in concentration in neurons and NDEs for months after acute TBI, are etiological contributors to CTE by either direct actions or by recruiting neurotoxic forms of Aβ peptides or P-tau. Such progression factors also may be useful new targets for development of drugs to prevent CTE.

Language: en

Keywords

Alzheimer disease; amyloid; cellular prion protein; phospho-tau; synaptogyrin-3