AIMS: The present study evaluated the combined treatment effects of aerobic exercise and antioxidative stress on moderate-stage Alzheimer's disease (AD).

METHODS: Ten-month-old APP/PS1 mice were given antioxidative treatment with acetylcysteine, along with aerobic exercise for 6 weeks. Spatial learning and memory were tested using the Morris water maze, and β-amyloid (Aβ) plaque deposits in the forebrain were quantified by Thioflavin-S staining. Levels of soluble Aβ1-42, β-secretase enzyme, ү-secretase enzyme, oxidative and antioxidant stress markers nitrotyrosine and peroxiredoxin-1, glial markers glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1, and synaptic protein synaptophysin in the hippocampus were all measured by western blotting and/or immunohistochemistry.

RESULTS: APP/PS1 mice showed severe declines in spatial learning and memory compared with their wild-type littermates, which were not attenuated by aerobic exercise combined with antioxidative treatment. The pathologic analysis revealed that Aβ deposition and production, oxidative stress, glial inflammation, and synaptic loss were not mitigated in the brain of exercised APP/PS1 mice, compared with the sedentary APP/PS1 animals.

CONCLUSION: This study reveals that a combined treatment of aerobic exercise plus antioxidative stress does not counteract pathophysiology in the moderate- or mid-stages of AD.