Background and aims: The APOE epsilon 4 genotype has a higher risk for developing coronary artery disease (CAD), but there is preliminary evidence that antioxidative lifestyle factors interact with... Show moreBackground and aims: The APOE epsilon 4 genotype has a higher risk for developing coronary artery disease (CAD), but there is preliminary evidence that antioxidative lifestyle factors interact with APOE genotype on CAD risk. Here, we assessed the effect modification of physical activity, oily fish and polyunsaturated fatty acid (PUFA) intake with APOE genotype on risk of incident CAD. Methods: The present study comprised 345,659 white European participants from UK Biobank (mean age: 56.5 years, 45.7% men) without a history of CAD. Information regarding physical activity, oily fish intake and PUFA intake was collected through questionnaires, and information on incident CAD through linkage with hospital admission records. Analyses were performed using Cox proportional hazard models adjusted for age and sex. Results: Higher physical activity level and oily fish intake were both associated with a lower incidence of CAD. However, these associations were similar across the different APOE genotypes (p-values for interaction > 0.05). Most notable, higher PUFA intake was associated with a lower CAD risk in APOE epsilon 4 genotype carriers (hazard ratio: 0.76, 95% confidence interval: 0.63-0.92), and not in APOE epsilon 3/epsilon 3 genotype carriers (0.90; 0.79, 1.02), but without statistical evidence for effect modification (p-valueinteraction = 0.137). Conclusions: While higher physical activity and high fish and PUFA intake were associated with a lower risk of incident CAD, no evidence for interaction of these lifestyle factors with APOE genotype was observed in UK Biobank participants. Interventions intended to reduce cardiovascular risk might therefore be similarly effective across the APOE genotype carriers. Show less
The APOE-epsilon 4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and... Show moreThe APOE-epsilon 4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and inflammation among APOE-epsilon 4 carriers, we aimed to examine whether BBB dysfunction and inflammation contribute to the relationship between APOE and AD key pathologies, as measured in the cerebrospinal fluid (CSF). We applied bootstrapped regression and path analyses involving Q-albumin CSF/plasma ratio (a BBB/blood-CSF barrier function marker), interleukins (IL-1 beta, IL-6, and IL-12p70; inflammation markers), and CSF p-Tau(181) and amyloid-beta(1-42) (AD pathology markers) of 97 participants (aged 38-83 years) from a university memory clinic. Our results showed that relationship between BBB dysfunction and AD pathology is modulated by IL-6 and these associations appear to be driven by the APOE-epsilon 4 genotype. This suggests that APOE-epsilon 4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD. (C) 2019 The Author(s). Published by Elsevier Inc. Show less
