P4–011: Effect of Treadmill Running on Soluble Beta‐amyloid Concentrations in Brains of Young Tg2576 Mice

During Alzheimer's disease (AD) pathogenesis, soluble amyloid beta (Aβ) aggregates into soluble oligomers and insoluble plaques in a concentration-dependent manner. Both physical activity and environmental enrichment, including cognitive enrichment alone and cognitive enrichment plus physical activity, have been demonstrated to delay the onset and progression of amyloid plaque formation in transgenic mouse models of AD. The purpose of this study was to determine whether or not a program of treadmill running would lead to reduced soluble Aβ concentrations in Tg2576 mice prior to the age of onset of amyloid plaque formation. Animals were housed in fully enriched environments, containing multi-levels, crawl spaces, and toys. The exercise group (n=8) ran on a level, motor driven treadmill at 15 m/min for one hour per day, five days a week, for 14 weeks beginning at three months of age. The sedentary group (n=8) was placed on an immobilized treadmill for the same amount of time. Animals were sacrificed at 6 months of age, and brain and soleus muscles were extracted. Soluble Aβ x-40 and Aβ x-42 concentrations were determined by sandwich ELISA following TBS extraction from sonicated hemibrains. Citrate synthase activity in soleus muscle was determined to assess muscle oxidative capacity, an indicator of effectiveness of an exercise training program in improving physical fitness. Citrate synthase activity was elevated by 20.5% (P<0.05) in the exercise group indicating the intensity of the exercise program was sufficient to elicit a training effect. Soluble Aβ x-40 and Aβ x-42 concentrations were 39.3% (P<0.01) and 22.1% (P<0.01) lower, respectively in the cognitively enriched, exercise trained animals than in cognitively enriched animals that did not exercise. These data are the first to demonstrate that exercise training, independent of cognitive enrichment, reduces soluble Aβ concentrations in the brains of a transgenic AD mouse model at an age prior to the onset of plaque.