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

Molecular & Cellular Toxicology 2019년 15권 4호 p.353 ~ 368
 ( Jamerlan Angelo ) - Gachon University Gachon Bionano Research Insitute Department of Bionanotechnology

 ( Dominguez Jacqueline ) - St. Luke’s Medical Center Institute for Neurosciences
 ( Ligsay Antonio ) - St. Luke’s Medical Center Department of Clinical Research
 ( Youn Young-Chul ) - Chung-Ang University College of Medicine Department of Neurology
 ( An Seong-Soo A. ) - Gachon University Gachon Bionano Research Insitute Department of Bionanotechnology
김상윤 ( Kim Sang-Yun ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Neurology

Abstract


Purpose of review: 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.

Recent findings: 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.

키워드

Animal models; Axial diffusivity; β-amyloid; Chronic traumatic encephalopathy; CSF; Diffusor tensor imaging; Fluid biomarkers; Neuroimaging; Neurofibrillary tangles; Plasma; Traumatic brain injury
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