Brayne C, Harrington C R, Wischik C M, Huppert F A, Chi L Y, Xuereb J H, O'Connor D W, Paykel E S
Department of Community Medicine, University of Cambridge, UK.
Dementia. 1996 May-Jun;7(3):169-74. doi: 10.1159/000106873.
An increased apolipoprotein E (ApoE) type epsilon 4 allele frequency is associated with both sporadic and familial late-onset Alzheimer's disease (AD). The age of onset of disease in patients homozygous for the epsilon 4 allele appears to be decreased by approximately 15 years compared with E2/3 individuals. In order to assess the influence of this allele on both dementia and cognitive decline in the elderly we have determined the ApoE genotype of 150 individuals over the age of 75 years who have taken part in a longitudinal study. Homozygosity for the epsilon 4 allele was rare. Of the 2 homozygotes, 1 was severely demented but the other did not receive a clinical diagnosis of dementia. The latter individual did demonstrate marked cognitive decline over a 28-month period. There was a consistent association between the presence of an epsilon 4 allele and both the clinical diagnosis of dementia and cognitive decline. These findings confirm a genetic heterogeneity in late-onset sporadic AD and prompt caution in the use of ApoE genotype to predict an elderly individual's susceptibility to either dementia or cognitive decline.
载脂蛋白E（ApoE）ε4等位基因频率增加与散发性和家族性晚发性阿尔茨海默病（AD）均相关。与E2/3个体相比，ε4等位基因纯合子患者的发病年龄似乎提前了约15年。为了评估该等位基因对老年人痴呆和认知衰退的影响，我们确定了参与一项纵向研究的150名75岁以上个体的ApoE基因型。ε4等位基因纯合子很少见。在这2名纯合子中，1名患有严重痴呆，另1名未得到痴呆的临床诊断。后者在28个月期间确实出现了明显的认知衰退。ε4等位基因的存在与痴呆的临床诊断和认知衰退之间存在一致的关联。这些发现证实了晚发性散发性AD中的遗传异质性，并提示在使用ApoE基因型预测老年人患痴呆或认知衰退的易感性时应谨慎。
