Lack of association of apolipoprotein E allele ϵ4 with late‐onset Alzheimer's disease among Finnish centenarians
Lack of association of apolipoprotein E allele ϵ4 with late‐onset Alzheimer's disease among Finnish centenarians
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芬兰百岁老人中载脂蛋白 E 等位基因 ϵ4 与迟发性阿尔茨海默病之间缺乏关联
作者：
E. Sobel;J. Louhija;R. Sulkava;Z. Davanipour;K. Kontula;H. Miettinen;M. Tikkanen;K. Kainulainen;R. Tilvis
文章摘要-在芬兰百岁老人中未发现阿尔茨海默病（AD）与载脂蛋白E-14型（ApoE-14）表型之间的关联（N = 179）。这些数据是基于1991年对芬兰所有百岁老人的调查。所有考试均在1991年进行。痴呆和AD的诊断以临床为依据，符合DSM-III-R和NINCDS-ADRDA标准。在358个等位基因中，有31个等位基因在百岁老人中检出，占8.7%。这一比例明显低于芬兰年轻人口的比例。179例百岁老人中有30例（16.8%）为β 4等位基因携带者。百岁老人中有151人（84.4%）是妇女。28名女性（18.5%）至少有一个等位基因，两名男性（7.1%）也是如此。临床诊断AD的患病率为26.8%; 44%的受试者认知正常，23%有认知下降或最多轻度痴呆（无鉴别诊断）的迹象，6%的痴呆临床诊断为AD以外的原因。对于AD病例与认知正常受试者，与成为α 4等位基因携带者相关的比值比为1.34（p = 0.64; 95%CI = [0.5，3.31]）。在女性中，比值比为0.99（p = 1.0; 95% CI = [0.4，2.6]）。在认知功能下降或至多轻度痴呆的受试者中（12.2%），有较少的，但不显着，比认知功能正常的受试者（16.5%）中，携带者。AD患者的96个等位基因中有10个（10.4%）为等位基因4，认知正常者的等位基因中有8.9%（14/158）为等位基因4。这种差异非常不显著。只有一个人是纯合子的等位基因。她的认知能力很正常。在这项研究的28名男性中，只有两名男性携带有α 4等位基因;因此，对男性的分析几乎没有效力。这些结果清楚地表明，即使接近（当前）生命的年龄上限，α 4等位基因也不一定导致AD。当结合以前的研究结果，这些结果表明，与AD的ApoE等位基因的关联可能是年龄依赖性的，ApoE等位基因可能会加速AD痴呆的过程，而不是一个直接的病原体或易感的遗传因素。
Article abstract—No association between Alzheimer's disease (AD) and apolipoprotein E type ϵ4 (ApoE ϵ4) phenotype was found among centenarians in Finland (N = 179). The data are based on ascertainment of all centenarians in Finland in 1991. All examinations were conducted during 1991. The diagnoses of dementia and AD were based on clinical grounds, conforming to DSM-III-R and NINCDS-ADRDA criteria. The percentage of ApoE ϵ4 alleles among the centenarians was 8.7% (31 of 358 alleles). This is significantly lower than percentages found in younger Finnish populations. Thirty (16.8%) of the 179 centenarians were ϵ4 allele carriers. One hundred fifty-one (84.4%) of the centenarians were women. Twenty-eight (18.5%) of the women had at least one ϵ4 allele, as did two (7.1%) of the men. The prevalence of clinically diagnosed AD was 26.8%; 44% of the subjects were cognitively normal, 23% had signs of cognitive decline or at most mild dementia (with no differential diagnosis), and 6% had a dementia clinically diagnosed as being due to some cause other than AD. For AD cases versus cognitively normal subjects, the odds ratio associated with being a carrier of the ϵ4 allele was 1.34 (p = 0.64; 95% CI = [0.5, 3.31). Among women, the odds ratio was 0.99 (p = 1.0; 95% CI = [0.4, 2.6]). There were fewer, but not significantly so, ϵ4 carriers among subjects with cognitive decline or at most mild dementia (12.2%) than there were among the cognitively normal subjects (16.5%). Ten (10.4%) of the 96 alleles belonging to AD cases were ϵ4, and 8.9% (14/158) of the alleles belonging to the cognitively normal subjects were ϵ4. This difference is highly nonsignificant. There was only one individual who was homozygous for the ϵ4 allele. She was cognitively normal. Among the 28 men in the study there were only two carriers of the ϵ4 allele; consequently, analyses for men have little power. These results clearly show that the ϵ4 allele does not necessarily lead to AD even near the (current) upper age-limit of life. When combined with previous findings, these results suggest that the association of the ApoE ϵ4 allele with AD may be age-dependent and that the ApoE ϵ4 allele might accelerate the AD dementing process rather than be a direct etiologic agent or a predisposing genetic factor.