Neuroinflammation and the APOε genotype: Implications for Alzheimer's disease and modulation by dietary flavonoids and n-3 polyunsaturated fatty acids

Abstract

Alzheimer's disease (AD) is the most common type of dementia with its pathology considered to be the result of complex interactions between genetic and environmental factors. Amongst a large variety of genes analysed, the APO epsilon genotype, represents the only firmly established common genetic risk factor for dementia, with the APOε4 carriers being at 3–16 fold increased risk of AD. Although, the mechanisms by which APOε genotype impacts on AD progression are not fully understood, recent evidence suggests that a large component of the increased risk associated with an APOε4 genotype is likely to be due to increased neuroinflammation and the subsequent loss of cognitive functions. There is increasing evidence from human epidemiological and rodent studies that the consumption of flavonoid-rich foods and n-3 polyunsaturated fatty acids can beneficially influence normal cognitive function. Investigation of the underlying physiological and molecular mechanisms indicates a positive impact of these dietary components on neurogenesis and neuroinflammation. This review will summarise the evidence of the impact and mechanisms underlying the impact of APOε genotype on dementia and AD and the potential role of dietary flavonoids and n-3 polyunsaturated fatty in modulating neuroinflammation and neurocognitive performances. Examination of molecular targets is suggestive that increased intakes of these dietary components have the potential alone or in an additive fashion to ameliorate the pathological consequences of the APOε4 allele. However research examining the ability of dietary strategies in this large population genotype subgroup is distinctly lacking.