The Neurobiology and Age-Related Prevalence of the ε4 Allele of Apolipoprotein E in Alzheimer's Disease Cohorts

le Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by amyloid beta (A beta) plaques and tau neurofibrillary tangles in the brain. Human apolipoprotein E (ApoE) is a lipid transport protein coded by the polymorphic APOE gene, with three major alleles: epsilon 2, epsilon 3 and epsilon 4. After age, the epsilon 4 allele is the greatest risk factor for developing sporadic AD, conferring an increased risk of 3-4 and 8-12 times for one or two copies of the allele, respectively. This risk is reported to vary by demographic factors including sex, ethnicity and geography. In order to understand the risk of ApoE epsilon 4 in relation to age, the primary risk factor for developing AD, we need to understand how the prevalence of APOE genotypes changes with age. Here, we present the first data on age-related prevalence of APOE epsilon 4 in AD in three AD cohorts in Australia and the USA. There is a significant association between age and epsilon 4 prevalence, particularly for epsilon 4 homozygotes, such that as age increases the prevalence of epsilon 4 decreases. Further studies on a random, population-based samp of the population are needed to provide more generalizable data, particularly in the > 90-year-old age group.