Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (life-style) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case-control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5'-lipoxygenase (5'-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A-allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p<0.0001), while AA genotype does so 1.79-fold (p<0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age.

Department of Epidemiology and Public Health Faculty of Medicine University of Ostrava Czech Republic

Discipline Anatomy and Histology and Bosch Institute School of Medical Sciences Sydney Medical School University of Sydney NSW 2006 Australia

Institute of Animal Physiology and Genetics Academy of Sciences Veveří 97 602 00 Brno Czech Republic

Laboratory of Neurobiology and Molecular Psychiatry Department of Biochemistry Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic

Physiologie de la Nutrition et Toxicologie UMR U866 INSERM Université de Bourgogne Agro Sup 6 Boulevard Gabriel Dijon 21000 France

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