Current fluid biomarkers, animal models, and imaging tools for diagnosing chronic traumatic encephalopathy

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that results from repetitive traumatic brain injury (TBI), whether mild or severe. Several popular sports that subject the head to impact have been linked as a primary cause of the disease. Phosphorylated tau and Aβ deposits are the two proteins observed histopathologically in CTE patients. An ischemic environment is created that contributes to the hyperphosphorylation of tau following traumatic brain injury. The use of fluid biomarkers, animal models for TBI, as well as imaging tools are considered valuable in understanding the pathophysiological mechanism of CTE. This review gives particular attention to the characteristics, advantages, and disadvantages of the current fluid biomarkers, use of animal models, and imaging techniques used in CTE diagnosis. Beta-amyloid and phosphorylated tau were suggested as the two main pathological biomarkers for chronic traumatic encephalopathy (CTE) diagnosis, though research into other fluid biomarkers of traumatic brain injury (TBI) such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and C-C motif chemokine 11 (CCL11) has been undertaken but was mostly limited by sample size, and decreased sensitivity in follow-up studies. Animal models and devices that simulate TBI were valuable in exploring injury dynamics and the role it may have on CTE. The use of transgenic animals in CTE research has also uncovered the different risk genes that may enhance CTE pathology. Magnetic resonance imaging (MRI), functional MRI and positron emission tomography (PET) imaging showed enough resolution to accurately diagnose CTE. However, diffusion tensor imaging (DTI) was able to identify microstructural changes in professional boxers that were not apparent in MRI. Currently, a single biomarker or imaging technique is not enough to accurately diagnose CTE and diagnostic accuracy is significantly enhanced when these different parameters are combined.