APOE genotype:: No influence on galantamine treatment efficacy nor on rate of decline in Alzheimer's disease
APOE genotype:: No influence on galantamine treatment efficacy nor on rate of decline in Alzheimer's disease
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DOI：
10.1159/000051238
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发表时间：
2001-03-01
影响因子：
2.4
通讯作者：
Parys, W
中科院分区：
文献类型：
--
作者：
Aerssens, J;Raeymaekers, P;Parys, W
载脂蛋白 E (APOE) 已被广泛证明是阿尔茨海默病 (AD) 的遗传风险因素。据报道，APOE 基因型与 AD 发病年龄、衰退速度和治疗反应有关。本研究旨在在大量 AD 患者研究人群中检验这些假设。 APOE 基因型是从 1,528 名白人受试者中确定的，这些受试者根据 NINCDS/ADRDA 标准诊断为可能的 AD 患者，参加了四项为期 3-12 个月的国际安慰剂对照临床试验，旨在评估加兰他敏或沙贝鲁唑治疗的疗效。除了患者人口统计数据和简易精神状态检查的基线分数外，还在研究开始、期间和结束时记录了痴呆症残疾评估 (DAD) 和阿尔茨海默病评估量表 (ADAS-cog) 认知分量表的分数。与其他 APOE 基因型的患者相比，APOE epsilon4 纯合子的发病年龄显着较低。与男性相比，epsilon4 等位基因在女性以及有 AD 家族史的受试者组中明显过多。根据 504 名接受安慰剂治疗的 AD 患者的纵向数据，ADAS-cog 量表上评分的线性年变化率为 5 分，DAD 量表上的线性年变化率为 11 分。 epsilon4 等位基因拷贝数不影响这些下降率。与安慰剂治疗组相比，沙贝鲁唑治疗在整个组中均无效，在按 epsilon4 等位基因计数分层的任何亚组中也无效。加兰他敏可改善认知和功能，且不受 epsilon4 等位基因计数的影响。总之，我们的数据证实了 epsilon4 纯合子与 AD 发病年龄之间存在很强的相关性，但不支持 epsilon4 等位基因拷贝数对认知和功能下降率的影响，也不支持对 AD 患者加兰他敏的疗效的影响。版权所有 (C) 2001 S. Karger AG，巴塞尔。
Apolipoprotein E (APOE) has been extensively demonstrated to be a genetic risk factor for Alzheimer's disease (AD). Associations of APOE genotype have been reported with age at AD onset, rate of decline, and responsiveness to therapy. This study aimed to test these hypotheses in a large study population of AD patients. APOE genotype was determined from 1,528 Caucasian subjects, diagnosed by NINCDS/ADRDA criteria as probable AD patients, enrolled in four international placebo-controlled clinical trials of 3-12 months duration, designed to evaluate efficacy of treatment with galantamine or sabeluzole. In addition to patient demographics and baseline scores for Mini Mental State Examination, scores on the Disability Assessment for Dementia (DAD) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) were recorded at the start, during, and at the end of the study. APOE epsilon4 homozygotes had a significantly lower age at disease onset compared to patients with other APOE genotypes. The epsilon4 allele was significantly over-represented in females compared to mates, and in the group of subjects with an AD family history. Based on longitudinal data of 504 placebo-treated AD patients, the linear annual rate of change in score was 5 points on the ADAS-cog scale and 11 on the DAD scale. The epsilon4 allele copy number did not influence these rates of decline. Sabeluzole treatment was not effective in the overall group compared to the placebo-treated group, nor in any subgroup stratified by epsilon4 allele count. Galantamine produced cognitive and functional improvement that were not affected by epsilon4 allele count. In conclusion, our data confirm a strong association between epsilon4 homozygotes and age at onset of AD but do not support an effect of epsilon4 allele copy number on rate of cognitive and functional decline nor on the efficacy of galantamine in patients with AD. Copyright (C) 2001 S. Karger AG, Basel.