Tau imaging in traumatic encephalopathy and dementia.

Objectives 1. Describe the neurodegenerative pathology in dementia and traumatic encephalopathy. 2. Describe radiotracers as biomarkers of tauopathies. 3. Illustrate patterns of tau imaging in traumatic encephalopathy and dementia, and correlate these with 18-FDG, amyloid imaging, and structural imaging.

Methods Repetitive brain injury leads to chronic traumatic encephalopathy, CTE. Its pathology overlaps Alzheimers dementia, AD (1). Both conditions show neurodegeneration with characteristic macromolecular depositions detected in histology, such as tau and amyloid complexes. These complexes are putative targets for biomarkers in PET brain imaging. We combine a PubMed search on imaging of CTE and AD covering the year 2015 with local studies done as part of the Alzheimers Disease Neuroimaging Initiative and imaging of CTE in former football players to generate an educational exhibit.

Results Tracers that are available for PET imaging in the clinic or in late clinical trials show promise in detecting an in vivo molecular signature that is useful in managing patients suffering from dementia and CTE. 18-F fluobetapir is an example of a commercially available agent that detects brain amyloid and assists in the diagnosis of clinically equivocal AD. In research it has been used to also detect amyloid in CTE. 18-F-AV-1451, is an investigational drug specific for tau complexes (neurofibrillar tangles) seen in AD and CTE (2). The distribution of tau related complexes is different in these conditions. In CTE it is diffuse in the neocortex while in AD it is largely in the medial temporal lobe (1,2). Tau imaging should increase specificity in the PET imaging of dementia and related conditions because normal brain (which may exhibit amyloid deposition with aging) does not accumulate tau complexes.

Conclusions The cross road between CTE and AD provides a unique substrate to review the histopathology of neurodegeneration, and the tracers based on these findings. These agents supplement markers of metabolism and amyloid deposition already available in the clinic. This expanded toolkit in brain PET imaging is expected to assist in the diagnosis of CTE and AD, provide risk stratification, and follow up response in new therapies. 1) Kiernan, Patrick T., Philip H. Montenigro, Todd M. Solomon, and Ann C. McKee. “Chronic Traumatic Encephalopathy: A Neurodegenerative Consequence of Repetitive Traumatic Brain Injury.” Seminars in Neurology 35, no. 1 (February 2015): 20-28. doi:10.1055/s-0035-1545080. 2) James, Olga G., P. Murali Doraiswamy, and Salvador Borges-Neto. “PET Imaging of Tau Pathology in Alzheimer’s Disease and Tauopathies.” Frontiers in Neurology 6 (March 9, 2015). doi:10.3389/fneur.2015.00038. RESEARCH SUPPORT: None