Early Changes in Memory, Motor Coordination and Strength in the Transgenic Rat Model of Alzheimer’s Disease, TgF344-AD

Introduction: Alzheimer’s disease (AD) is the most common form of dementia and an estimated 5.7 million American’s are currently suffering from this disease resulting in $277 billion in health care costs as of 2018. As the number of cases and cost are expected to double by 2050, new approaches are needed to properly identify at-risk individuals prior to irreversible changes to the brain caused by this disease. Purpose: Through the use of a novel rodent model, this study assessed early changes in muscular coordination and strength relative to cognitive decline due to AD, as well as providing insight into the progression of these changes and whether sex differences exist within AD development. Hypothesis: Declines in muscular coordination and strength will precede cognitive decline. Males will exhibit significantly worse declines among all measures earlier than females. Methods: Thirty-eight TgF-344AD rats were compared to 38 wild type (WT) TgF-344 rats for muscle atrophy (grip strength test), coordination (rotarod), and spatial memory (Morris Water Maze test). Testing periods occurred at 3, 6, and 9 m and body weight was measured prior to assessments for these time periods. Statistical Analysis: Repeated measures ANOVA was used to identify within group differences. Mixed model 2-way ANOVA (group x age) with a Bonferroni post hoc test was used to identify any significant effects. ANOVA with a Tukey post hoc was used to determine between group differences. Unpaired independent T-tests were used to determine the degree of significance based on significant P-values (p≤0.05) determined by the Tukey post hoc test. Results: AD males displayed significantly heavier body weight at 3 m, 6 m, and 9 m and AD females displayed significantly heavier body weight at 6 m and 9 m compared to the WT cohort. No significant difference was seen in grip strength between any groups. AD females and AD males expressed a significant decline in motor coordination at 6 m but by 9 m all groups expressed a significant decline in motor coordination. No significant difference was seen in motor coordination between groups. The AD group as a whole displayed significantly worse memory function at 9 m compared to WT group. Conclusion: Body weight may be a risk factor for developing AD. AD may cause an accelerated rate of decline in motor coordination. Memory dysfunction precedes deficits in strength and coordination. No AD-related sex differences were identified but 2-way ANOVA identified a significant effect for AD females on motor coordination decline seen at 6 m but not males