APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study

Abstract

Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO₂Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO₂Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population.

Keywords: APOE; Aerobic exercise; African Americans; BDNF; Mild cognitive impairment; Oxygen consumption.

Figure 1

Box plot of percent (%) change in VO₂Max from baseline values, after 6 months of exercise training (a) between exercise groups, (b) between genders, and (c) between non-ε4 and ε4 carriers. Middle line in box represents the median; lower box bounds the first quartile; upper box bounds the 3^rd quartile. Whiskers represent the 95% confidence interval of the mean. Open circles are outliers from 95% confidence interval. *Significant difference between groups (P=0.024). Non-ε4 = non carriers of the APOE ε 4 allele, ε4 = carrier of the APOEε4 allele.

Figure 2

Box plot of percent (%) change in serum levels of BDNF from baseline values, after 6 months of exercise training (a) between exercise groups, (b) between genders, (c) between non-ε4 and ε4 carriers and (d) between non-ε4 and ε4 carriers only within the aerobic exercise group. Middle line in box represents the median; lower box bounds the first quartile; upper box bounds the 3^rd quartile. Whiskers represent the 95% confidence interval of the mean. Open circles are outliers from 95% confidence interval. *Significant difference between groups (P=0.016 and P=0.021 for C and D respectively). Non-ε4 = non carriers of the APOE ε 4 allele, ε4 = carrier of the APOEε4 allele.