APOE ε4 genotype modulates the relationship between fatty acids consumption and brain connectivity

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Abstract
Background: Lipoproteins play a crucial role in the brain, where they assist in lipid transport, as lipids constitute a majority of the brain’s dry mass. The apolipoprotein E (APOE) ε4 gene allele carriage promotes lipid dysfunction, endothelial injury and cerebrovascular disease, contributing to increased risk of dementia. Furthermore, it also results in insufficient lipid availability for neuronal remodelling and repair processes, leading to altered synaptogenesis and neurogenesis. In this scenario, we explored the relationship between the consumption of various kinds of fatty acids and functional brain connectivity in carriers and non‐carriers of this genetic risk factor.Method: 64 individuals (24 APOE ε4+; 40 APOE ε4‐) at high cardiovascular risk (waist/height index ≥0.5), aged 50 and above and without cognitive impairment underwent four minutes of eyes‐closed resting state magnetoencephalography recording. We estimated functional connectivity using phase‐locking value and applied data driven cluster‐based permutation test to detect the brain regions for which mean connectivity with every other region across the brain was modulated by each of four fatty acids consumption variables: consumption of monounsaturated fatty acids, consumption of saturated fatty acids, ω‐3/ω‐6 fatty acids consumption and overall quality of fatty acids consumption [(monounsaturated+polyunsaturated)/saturated].Result: None of the studied variables yielded significant results across the whole sample. However, an interesting result emerged after stratification by genotype:‐ higher consumption of monounsaturated fatty acids was associated with lower functional connectivity in the theta (temporal cluster) and delta bands (frontal cluster).‐ higher ω‐3/ω‐6 consumption ratios were associated with lower functional connectivity in the alpha band (occipital cluster).Conclusion: ε4 carriers seem to benefit from greater ω‐3/ω‐6 consumption, which was found to be associated to lower connectivity in the alpha band. Relevantly, several studies point towards alpha hyperconnectivity as a early sign of dysfunction in healthy individuals at high risk for Alzheimer’s disease. On the other hand, for ε4 non‐carriers, where lipid transportation within the brain is expected to be optimal, monounsaturated fatty acids appear to be more beneficial.