The Effect of Repetitive Mild Traumatic Brain Injury on an Alzheimer’s Mouse Model

Kristen Marie Craven

Major Professor: Jane M Flinn, PhD, Department of Psychology

Committee Members: Craig McDonald, Geraldine Grant

David King Hall, #2027
April 17, 2019, 11:00 AM to 01:00 PM

Abstract:

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting nearly 6 million individuals in the United States alone. The hallmarks of AD include declines in spatial and short-term memory as well as the build-up of amyloid plaques and tau tangles. It is well documented that traumatic brain injury (TBI) is a risk factor for Alzheimer’s disease. However, the effect of repetitive mild TBI on adolescent AD mice has yet to be studied. This work determined the effect of repetitive mild TBI, 5 hits with 48 hour intervals, on 8-week old mice containing genes for amyloid precursor protein (APP) and tau. Following the last TBI, mice were assessed on spatial memory, anxiety, and motor ability. Additionally, these mice were tested again at 3.5 months old, when tau tangles are known to be present. Alzheimer’s mice demonstrate spatial memory deficits compared to Wildtype mice as evidenced by a slower time to platform, less time spent in target quadrant, and fewer platform crosses on probe trials in Morris Water Maze. Additionally, AD mice spend more time near the edges of the pool, indicating anxiety. This effect is corroborated by open field results that demonstrate that AD mice spend significantly less time in the center of the maze. Elevated zero results show that AD mice subjected to TBI have significantly more head-dips than Wildtype mice subjected to rmTBI, demonstrating increased risk-taking behavior. Finally, biochemical assays were utilized to assess levels of inflammatory markers, such as glial fibrillary acidic protein, as well as plaque and tangle pathology. Overall, AD mice demonstrate higher levels of inflammatory makers than Wildtype mice. This study gives a more comprehensive view into the effect that repetitive mild TBIs early in life has on the progression of AD.