Abstract
Extensive research supports the use of exercise to protect against Alzheimer’s disease (AD). Nevertheless, there is limited evidence from human studies regarding the mechanisms underlying the positive effects of exercise on the brain. Gene expression determines the extent to which a gene is ‘turned on or off’ and can be used to understand mechanistic pathways. Animal research has demonstrated that exercise influences the expression of genes related to various AD biological pathways; however, the impact of exercise on AD-related gene expression has not yet been studied in humans. PURPOSE: To examine changes in AD-related gene expression following a six-month high-intensity exercise intervention. METHODS: Cognitively normal men and women (60-80y) were randomised to either six-months of work-matched high-intensity exercise (n=33), moderate-intensity exercise (n=34) or an inactive control group (n=32). Blood samples were collected pre- and post-intervention and expression levels from a panel of genes implicated in AD were measured. Analysis of covariance (covaried for age and gender), with adjustment for multiple comparisons, was conducted to determine group differences. RESULTS: Decreases in AD-related gene expression following six months of exercise, compared with the control group. More specifically, gene expression associated with cholesterol metabolism (ABCA1; p < 0.001), amyloid precursor protein processing (ADAM17, BACE1; p < 0.05) and synaptic plasticity (UCHL1; p < 0.001) was favourably altered in the high-intensity exercise intervention, compared with the moderate-intensity intervention and control groups. CONCLUSIONS: Investigation of AD-related gene expression has the potential to play an important role in understanding the biological pathways by which exercise reduces AD risk and contributes to enhanced cognitive health. The current work indicates a dose-dependent effect of exercise intensity on the expression of genes associated with AD, revealing mechanistic pathways that require further investigation.
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