In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury

Gorgoraptis, N. et al. (2019) In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury. Science Translational Medicine, 11(508), eaaw1993. (doi: 10.1126/scitranslmed.aaw1993)

Abstract

Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) ε4 genotype affected the relationship between flortaucipir binding and time since injury, CSF β amyloid 1–42 (Aβ42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.

• Item Type: Articles
• Additional Information: This project was funded by the Medical Research Council (MRC) UK grant number MR/L022141/1 (to D.J.S.). D.J.S. was supported by an NIHR Research Professorship (NIHRRP- 011-048). This work was supported by the UK Dementia Research Institute. Infrastructure was supported by the National Institute of Health Research (NIHR) Imperial Biomedical Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcleod, Mrs Claire and Maclean, Dr Linda and McMillan, Professor Tom
• Authors: Gorgoraptis, N., Li, L. M., Whittington, A., Zimmerman, K. A., Maclean, L. M., McLeod, C., Ross, E., Heslegrave, A., Zetterberg, H., Passchier, J., Matthews, P. M., Gunn, R. N., McMillan, T. M., and Sharp, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Science Translational Medicine
• Publisher: American Association for the Advancement of Science
• ISSN: 1946-6234
• ISSN (Online): 1946-6242
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Science Translational Medicine 11(508): eaaw1993
• Publisher Policy: Reproduced in accordance with the publisher copyright policy