Subchronic pathobiological response following chronic repetitive mild traumatic brain injury in an aged preclinical model of amyloid pathogenesis

Ojo, J. O., Leary, P., Lungmus, C., Algamal, M., Mouzon, B., Bachmeier, C., Mullan, M., Stewart, W. and Crawford, F. (2018) Subchronic pathobiological response following chronic repetitive mild traumatic brain injury in an aged preclinical model of amyloid pathogenesis. Journal of Neuropathology and Experimental Neurology, 77(12), pp. 1144-1162. (doi: 10.1093/jnen/nly101) (PMID:30395237)

Abstract

Repetitive mild traumatic brain injury (r-mTBI) is a risk factor for Alzheimer disease (AD). The precise nature of how r-mTBI leads to, or precipitates, AD pathogenesis remains unclear. In this study, we explore subchronic effects of chronic r-mTBI (12-impacts) administered over 1-month in aged-PS1/APP mice and littermate controls. We investigate specific mechanisms that may elucidate the molecular link between AD and r-mTBI, focusing primarily on amyloid and tau pathology, amyloid processing, glial activation states, and associated clearance mechanisms. Herein, we demonstrate r-mTBI in aged PS1/APP mice does not augment, glial activation, amyloid burden, or tau pathology (with exception of pS202-positive Tau) 1 month after exposure to the last-injury. However, we observed a decrease in brain soluble Aβ42 levels without any appreciable change in peripheral soluble Aβ42 levels. This was accompanied by an increase in brain insoluble to soluble Aβ42 ratio in injured PS1/APP mice compared with sham injury. A parallel reduction in phagocytic receptor, triggering receptor expressed on myeloid cells 2, was also observed. This study demonstrates very subtle subchronic effects of r-mTBI on a preexisting amyloid pathology background, which may be on a continuum toward a slow and worsening neurodegenerative outcome compared with sham injury, and therefore, have many implications, especially in the elderly population exposed to TBI.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stewart, Dr William
• Authors: Ojo, J. O., Leary, P., Lungmus, C., Algamal, M., Mouzon, B., Bachmeier, C., Mullan, M., Stewart, W., and Crawford, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Neuropathology and Experimental Neurology
• Publisher: Oxford University Press
• ISSN: 0022-3069
• ISSN (Online): 1554-6578
• Published Online: 03 November 2018
• Copyright Holders: Copyright © 2018 American Association of Neuropathologists, Inc.
• First Published: First published in Journal of Neuropathology and Experimental Neurology 77(12): 1144-1162
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher