*Article* **ApoE Genotype-Dependent Response to Antioxidant and Exercise Interventions on Brain Function**

**Kiran Chaudhari 1, Jessica M. Wong 1, Philip H. Vann 1, Tori Como 2, Sid E. O'Bryant <sup>2</sup> and Nathalie Sumien 1,\***


Received: 29 May 2020; Accepted: 23 June 2020; Published: 25 June 2020

**Abstract:** This study determined whether antioxidant supplementation is a viable complement to exercise regimens in improving cognitive and motor performance in a mouse model of Alzheimer's disease risk. Starting at 12 months of age, separate groups of male and female mice expressing human Apolipoprotein E3 (GFAP-ApoE3) or E4 (GFAP-ApoE4) were fed either a control diet or a diet supplemented with vitamins E and C. The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure reflex and motor, cognitive, and affective function while remaining on their treatment. Subsequently, plasma inflammatory markers and catalase activity in brain regions were measured. Overall, the GFAP-ApoE4 mice exhibited poorer motor function and spatial learning and memory. The treatments improved balance, learning, and cognitive flexibility in the GFAP-ApoE3 mice and overall the GFAP-ApoE4 mice were not responsive. The addition of antioxidants to supplement a training regimen only provided further benefits to the active avoidance task, and there was no antagonistic interaction between the two interventions. These outcomes are indicative that there is a window of opportunity for treatment and that genotype plays an important role in response to interventions.

**Keywords:** ApoE; exercise; antioxidants; oxidative stress; cognition; motor; vitamin E; vitamin C; aging; Alzheimer's disease
