A cross-sectional examination of a family history of Alzheimer's disease and ApoE epsilon 4 on physical fitness, molecular biomarkers, and neurocognitive performance

Purpose: The present study examined whether the epsilon 4 allele of the apolipoprotein E (ApoE) gene impacts molecular biomarkers and neurocognitive performance among individuals at genetic risk for developing Alzheimer's disease (AD). The correlations between physical fitness and molecular/neurocognitive indices were also explored. Methods: Fasting blood samples were collected from 162 individuals with a family history of AD (ADFH). There were twenty-two carriers of the ApoE-4 variant (ApoE-4 group). For comparison purposes we randomly selected 22 non-E4 carriers (non-ApoE-4 group) from the ADFH individuals. Circulating inflammatory cytokines (e.g., TNF-alpha, IL-1 beta, IL-6, IL-8, and IL-15), neuroprotective growth factors (e.g., BDNF, IGF-1, IGF-2, VEGF, and FGF-2), and Amyloid-p peptides (e.g., A beta 1-40 and A beta 1-42), neurocognitive performance [e.g., behavior and brain evenrelated potentials (ERP)] during a task-switching paradigm, as well as physical fitness scores were measured. Results: The ApoE-4 group relative to the non-ApoE-4 group was similar with respect to molecular biomarkers, physical fitness, and most measures of neurocognitive performance. However, ADFH individuals that were E4 carriers exhibited significantly higher local switching accuracy costs, worse accuracy as well as smaller ERP P3 amplitudes for the memory-switching condition. Importantly, cardiorespiratory fitness levels were significantly correlated with accuracy for most task-switching conditions, and levels of BDNF, A beta 1-40, and A beta 1-42 collapsed across the two groups even when controlling for the age co-variable, while the ApoE-4 group revealed similar pattern of results. Conclusions: These data suggest that individuals with ADFH that were carriers of the ApoE-4 variant performed worse on the task-switching paradigm and that this could be due to compromised task-set and memory updating processes. Physical exercise interventions aimed to enhance cardiorespiratory fitness levels could be a potential AD prevention strategy for ameliorating cognitive function and reducing the accumulation of the A beta peptides in this high risk group.

Automated summary

Individuals with a family history of AD who were carriers of the ApoE-4 variant performed worse in the task-switching paradigm, potentially due to compromised task-set and memory updating processes. Physical exercise interventions aimed at enhancing cardiorespiratory fitness levels could be a potential strategy for AD prevention, improving cognitive function, and reducing the accumulation of A beta peptides in high-risk groups.