Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease

Purpose This study investigated the effect of treadmill running on cognitive declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD mice. Methods At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg-AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The AD + EX mice were subjected to treadmill running for 12 wk. At each pathological stage, the background strain mice were included as wild-type control (WT + CON, n = 8-12). Results At the early stage of AD, 3xTg-AD mice had impaired short- and long-term memory based on Morris water maze along with higher cortical A deposition, higher hippocampal and cortical tau pathology, and lower hippocampal and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the tau pathology along with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long-term memory along with higher levels of A deposition, soluble A(1-40) and A(1-42), tau pathology, and lower levels of brain-derived neurotrophic factor, PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the A and tau pathology along with suppression of the decreased synaptic proteins and brain-derived neurotrophic factor in the hippocampus and cortex. Conclusions The current findings suggest that treadmill running provides a nonpharmacological means to combat cognitive declines due to AD pathology.