Development of In Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury
Annual rept. 15 Jan 2014 - 14 Jan 2015
WASHINGTON UNIV ST LOUIS MO
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Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive neurological and psychiatric deterioration 1-9. This syndrome is termed chronic traumatic encephalopathy CTE 1, 7, 10, and is also known as dementia pugilistica 3, 11 or punch drunk syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain injuries 15-17 may also be at risk for this condition. Currently, there are no methods to identify progressive tau pathology in living humans. Hypothesis Aggregated forms of hyperphosphorylated tau protein formed acutely in the setting of traumatic brain injury can seed further aggregation of intracellular tau in nearby cells, leading to delayed propagation of tau pathology and neurodegeneration. Objective To develop standardized, high-throughput blood and cerebrospinal fluid assays for aggregated forms of tau responsible for propagation of tau pathology after traumatic brain injury. Progress to date To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing efforts include development of more sensitive methods to detect tau, and combinations of repetitive concussive TBI with binge ethanol administration. Substantial progress towards increasing the sensitivity of cell-based assays for tau aggregation activity has been made, and additional antibody-based tau detection methods for blood samples are in development.
- Medicine and Medical Research