INITIATION AND PROPAGATION STAGES OF BETA-AMYLOID ARE ASSOCIATED WITHDISTINCTIVE APOLIPOPROTEIN-E, AGE, AND GENDER PROFILES

Several recent studies have defined a relationship between apo-lipopro tein E (apoE) genotype and the risk of various neurodegenerative disor ders. However, few studies have examined the influence of apoE on quan titative measures of beta-amyloid (A beta) accumulation in a large pop ulation of autopsy cases. Using a multi-level analysis model, the inte rrelationships among apoE genotype, gender, age, and A beta accumulati on were investigated. In the population of these cases, there was a st rong relationship between the presence of an epsilon 4 allele and exte nt of A beta in the frontal and entorhinal cortex. That is, when evalu ating the presence or absence of significant A beta (> 1% A beta load) , subjects with one and two epsilon 4 alleles were 1.9 and 3.5 times m ore likely to have significant A beta accumulation than those with no epsilon 4 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 c ases with significant A beta (> 1% A beta load), the degree of A beta load was best predicted by the presence of an epsilon 2, allele and ge nder; females with no epsilon 2 alleles had the highest A beta loads ( mean = 12.3%), while males with one epsilon 2 allele had the lowest am ount of A beta accumulation (mean = 8.6%). Our results suggest that th e presence of an epsilon 4 allele predicts an earlier onset of A beta deposition that is independent of gender. In contrast, once A beta dep osition has been initiated, the presence of an epsilon 2 allele is ass ociated with slower rates of accumulation, with males benefiting from the protective effect more than females. (C) 1998 Elsevier Science B.V . All rights reserved.