APOE Genetic Variants and Cognitive Function in Older Men
As the U.S. population ages, there is growing concern about the loss of mental acuity that is common through aging and associated with high financial cost, loss of independence and mortality. It has been estimated that at least 10% of people 65 years or older and 50% of those ≥ 85 years old have some form of cognitive impairment, ranging from mild deficits to dementia.
Biomarkers that predict future risks are critical to design targeted prevention of cognitive decline. Apolipoprotein E (APOE) is a protein involved in transport of cholesterol and lipids throughout the body. It also mediates clearance of plasma lipoproteins and contributes to redistribution of lipids to cells.APOE ε4 allele, derived from the combination of polymorphisms rs429358 and rs7412, is the biomarker with the greatest known influence on the risk of developing Alzheimer's disease (AD). Nonetheless, the ε4 allele has been found to be "protective" for AD in specific age groups, such as younger ages that precede the bulk of AD diagnosis and in population older than 90 years old.
In addition to the single nucleotide polymorphisms (SNPs) used to define the epsilon alleles, two SNPs located in the promoter region of APOE have been described: rs449647 and rs405509. Evidence suggests that this region modulates transcriptional activity of APOE and that these polymorphisms may influence its effect on AD. Two studies in populations from Italy have found an increased frequency of the A/A genotype and A allele of rs449647 in AD. Bizarro et al., and Lescai et al., have reported higher frequencies of the G allele in rs405509 in AD than in controls (42.60% vs. 29.29%), whereas the frequency of the T allele for this polymorphism was lower in AD than in controls (32.5% vs. 48.0%). Polymorphism rs440446, located in intron 1 (enhancer), also affects transcriptional activity of APOE. However, the effect of polymorphisms rs449647, rs405509, rs440446 and their haplotypes on cognitive function in older populations has never been studied. In this study, we evaluated the influence five APOE polymorphisms, including the epsilon alleles, in modulating cognitive function in men between the ages of 49 and 97 years participating in the prospective VA (Veterans Affairs) Normative Aging Study cohort.
Background
As the U.S. population ages, there is growing concern about the loss of mental acuity that is common through aging and associated with high financial cost, loss of independence and mortality. It has been estimated that at least 10% of people 65 years or older and 50% of those ≥ 85 years old have some form of cognitive impairment, ranging from mild deficits to dementia.
Biomarkers that predict future risks are critical to design targeted prevention of cognitive decline. Apolipoprotein E (APOE) is a protein involved in transport of cholesterol and lipids throughout the body. It also mediates clearance of plasma lipoproteins and contributes to redistribution of lipids to cells.APOE ε4 allele, derived from the combination of polymorphisms rs429358 and rs7412, is the biomarker with the greatest known influence on the risk of developing Alzheimer's disease (AD). Nonetheless, the ε4 allele has been found to be "protective" for AD in specific age groups, such as younger ages that precede the bulk of AD diagnosis and in population older than 90 years old.
In addition to the single nucleotide polymorphisms (SNPs) used to define the epsilon alleles, two SNPs located in the promoter region of APOE have been described: rs449647 and rs405509. Evidence suggests that this region modulates transcriptional activity of APOE and that these polymorphisms may influence its effect on AD. Two studies in populations from Italy have found an increased frequency of the A/A genotype and A allele of rs449647 in AD. Bizarro et al., and Lescai et al., have reported higher frequencies of the G allele in rs405509 in AD than in controls (42.60% vs. 29.29%), whereas the frequency of the T allele for this polymorphism was lower in AD than in controls (32.5% vs. 48.0%). Polymorphism rs440446, located in intron 1 (enhancer), also affects transcriptional activity of APOE. However, the effect of polymorphisms rs449647, rs405509, rs440446 and their haplotypes on cognitive function in older populations has never been studied. In this study, we evaluated the influence five APOE polymorphisms, including the epsilon alleles, in modulating cognitive function in men between the ages of 49 and 97 years participating in the prospective VA (Veterans Affairs) Normative Aging Study cohort.