Voluntary running does not reduce neuroinflammation or improve non-cognitive behavior in the 5xFAD mouse model of Alzheimer's disease

Physical exercise has been suggested to reduce the risk of developing Alzheimer's disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse model of AD did not affect levels of soluble amyloid beta (Aβ), synaptic proteins or cognitive function. In this follow-up study, we investigate whether running could impact other pathological aspects of the disease, such as insoluble Aβ levels, the neuroinflammatory response and non-cognitive behavioral impairments. We investigated the effects of 24 weeks of voluntary wheel running in female 5xFAD mice (n = 30) starting at 2-3 months of age, before substantial extracellular plaque formation. Running mice developed hindlimb clasping earlier (p = 0.009) compared to sedentary controls. Further, running exacerbated the exploratory behavior in Elevated plus maze (p = 0.001) and anxiety in Open field (p = 0.024) tests. Additionally, microglia, cytokines and insoluble Aβ levels were not affected. Taken together, our findings suggest that voluntary wheel running is not a beneficial intervention to halt disease progression in 5xFAD mice.