Henderson A S, Easteal S, Jorm A F, Mackinnon A J, Korten A E, Christensen H, Croft L, Jacomb P A
National Health and Medical Research Council Social Psychiatry Research Unit, Australian National University, Canberra, Australia.
Lancet. 1995 Nov 25;346(8987):1387-90. doi: 10.1016/s0140-6736(95)92405-1.
From clinically based series it has been proposed that, in homozygotes for the apolipoprotein E epsilon 4 (apoE epsilon 4) allele, Alzheimer's disease is almost inevitable by the age of 80. A population sample of persons aged 70 years and over was interviewed in 1990-91 to ascertain the presence of dementia or cognitive impairment. The sample was reinterviewed in 1994, when the apoE genotype was also determined. Prevalence data for the 638 persons who completed the second examination revealed a linear association between having an apoE epsilon 4 allele and both dementia and cognitive impairment (for heterozygotes, odds ratio for dementia 1.89, 95% confidence interval 1.04-3.44 and for homozygotes OR 3.58, 95% CI 1.08-11.82; both adjusted for age). However, even in subjects homozygous for epsilon 4 the estimated prevalence of dementia by age 90 was only about 50%. Persons with one or two epsilon 4 alleles were more likely to have a family history of dementia than those with none. This study confirms in a population sample that the epsilon 4 allele is a risk factor for dementia, but refutes the suggestion that homozygosity for the epsilon 4 allele is sufficient for the development of Alzheimer's disease: persons with either one or two epsilon 4 alleles may reach late old age without cognitive impairment.
基于临床研究系列，有人提出，对于载脂蛋白Eε4（apoEε4）等位基因的纯合子而言，到80岁时患阿尔茨海默病几乎是不可避免的。1990 - 1991年对70岁及以上人群的一个样本进行了访谈，以确定是否存在痴呆或认知障碍。1994年对该样本进行了再次访谈，同时也确定了apoE基因型。完成第二次检查的638人的患病率数据显示，携带apoEε4等位基因与痴呆和认知障碍之间存在线性关联（对于杂合子，痴呆的优势比为1.89，95%置信区间为1.04 - 3.44；对于纯合子，优势比为3.58，95%置信区间为1.08 - 11.82；两者均根据年龄进行了调整）。然而，即使是ε4纯合子个体，到90岁时痴呆的估计患病率也仅约为50%。有一个或两个ε4等位基因的人比没有该等位基因的人更有可能有痴呆家族史。这项在人群样本中的研究证实，ε4等位基因是痴呆的一个风险因素，但反驳了ε4等位基因纯合足以导致阿尔茨海默病发生的观点：有一个或两个ε4等位基因的人可能在没有认知障碍的情况下活到高龄。
