Exercise improves cognition and hippocampal plasticity in APOE ε4 mice

Background: Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that epsilon 4 carriers may benefit from regular physical activity. Methods: We examined voluntary wheel-running, memory, and hippocampal plasticity in APOE epsilon 3 and APOE epsilon 4 transgenic mice at 10-12 months of age. Results: Sedentary epsilon 4 mice exhibited deficits in cognition on the radial-ann water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in epsilon 4 mice resulted in improvements on the RAWM to the level of epsilon 3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in epsilon 3 and epsilon 4 mice, and after exercise BDNF was similarly increased in both epsilon 3 and epsilon 4 mice. In sedentary epsilon 4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in epsilon 4 mice to the level of epsilon 3 mice, and in epsilon 4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function. Conclusions: Our results support the hypothesis that exercise can improve cognitive function, particularly in epsilon 4 carriers. (C) 2009 The Alzheimer's Association. All rights reserved.