Initiation and propagation stages of beta-amyloid are associated with distinctive apolipoprotein E, age, and gender...

Several recent studies have defined a relationship between apo-lipoprotein E (apoE) genotype and the risk of various neurodegenerative disorders. However, few studies have examined the influence of apoE on quantitative measures of beta-amyloid (Abeta) accumulation in a large population of autopsy cases. Using a multi-level analysis model, the interrelationships among apoE genotype, gender, age, and Abeta accumulation were investigated. In the population of these cases, there was a strong relationship between the presence of an epsilon4 allele and extent of Abeta in the frontal and entorhinal cortex. That is, when evaluating the presence or absence of significant Abeta (>1% Abeta load), subjects with one and two epsilon4 alleles were 1.9 and 3.5 times more likely to have significant Abeta accumulation than those with no epsilon4 alleles. These risks increased by a multiplicative factor of 1.014 for each year of age (at the time of death). In the subset of cases with significant Abeta (>1% Abeta load), the degree of Abeta load was best predicted by the presence of an epsilon2 allele and gender; females with no epsilon2 alleles had the highest Abeta loads (mean=12.3%), while males with one epsilon2 allele had the lowest amount of Abeta accumulation (mean=8.6%). Our results suggest that the presence of an epsilon4 allele predicts an earlier onset of Abeta deposition that is independent of gender. In contrast, once Abeta deposition has been initiated, the presence of an epsilon2 allele is associated with slower rates of accumulation, with males benefiting from the protective effect more than females.