Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E
Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E
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DOI：
10.1056/nejm199603213341202
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发表时间：
1996-03-21
影响因子：
158.5
通讯作者：
Osborne, D
中科院分区：
文献类型：
--
作者：
Reiman, EM;Caselli, RJ;Osborne, D
背景。两组中葡萄糖代谢的载脂蛋白的变体削减了葡萄糖代谢的区域速率。 e等位基因似乎是大多数晚期阿尔茨海默氏病的病例，并且具有两份Epsilon 4等位基因副本的人似乎具有痴呆症的高风险。正电子发射断层扫描（PET）已经确定了大脑的特定区域，其中葡萄糖代谢的速率逐渐下降，在可能的阿尔茨海默氏病患者中，我们使用PET研究了epsilon纯合受试者中的这些相同大脑的相同区域是否受到影响。 4在认知障碍发作之前的等位基因。在50至65岁的235名志愿者中建立了载脂蛋白E基因型，他们报告了可能的阿尔茨海默氏病，神经系统和精神病学评估，神经心理学测试，磁共振成像和PET的一部分，并在11 E4 HOMOGYOZYGOTES和22 e4 homozyozygotes中进行了启动。没有Epsilon 4等位基因，他们的性别，年龄和教育水平匹配。使用一种自动化方法来生成一个聚集的表面投射图，该图比较了两组中葡萄糖代谢的区域速率。 Epsilon 4纯合子在认知上正常，它们在同一后扣带回，顶叶，颞叶，时间和前额叶区域的葡萄糖代谢率显着降低，就像先前研究的患有阿尔茨海默氏病的患者中，它们在其他前期先前研究的患者中也降低了Glcosose hepose Operfrontalist的速率。在正常衰老期间可能会优先影响的区域。在中年后期，载脂蛋白E的纯合4等位基因的认知正常受试者在大脑的同一地区与可能的阿尔茨海默氏病的患者相同的葡萄糖代谢减少了这些发现，这些发现提供了Epsilon 4 4的存在证据。等位基因是阿尔茨海默氏病的危险因素，PET可能会提供一种相对较快的测试未来治疗方法以预防阿尔茨海默氏病。 （c）1996年，马萨诸塞州医学会。
Background. Variants of the apolipoprotein pared regional rates of glucose metabolism in the two groups. E allele appear to account for most cases of late-onset Alzheimer's disease, and persons with two copies of the epsilon 4 allele appear to have an especially high risk of dementia. Positron-emission tomography (PET) has identified specific regions of the brain In which the rate of glucose metabolism declines progressively in patients with probable Alzheimer's disease, We used PET to investigate whether these same regions of the brain are affected in subjects homozygous for the epsilon 4 allele before the onset of cognitive impairment.Methods. Apolipoprotein E genotypes were established in 235 volunteers 50 to 65 years of age who reported a family history of probable Alzheimer's disease, Neurologic and psychiatric evaluations, a battery of neuropsychological tests, magnetic resonance imaging, and PET were performed in 11 E4 homozygotes and 22 controls without the epsilon 4 allele who were matched for sex, age, and level of education. An automated method was used to generate an aggregate surface-projection map that compared regional rates of glucose metabolism in the two groups.Results. The epsilon 4 homozygotes were cognitively normal, They had significantly reduced rates of glucose metabolism In the same posterior cingulate, parietal, temporal, and prefrontal regions as in previously studied patients with probable Alzheimer's disease, They also had reduced rates of glucose metabolism in additional prefrontal regions, which may be preferentially affected during normal aging.Conclusions. In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease, These findings provide preclinical evidence that the presence of the epsilon 4 allele is a risk factor for Alzheimer's disease, PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease. (C) 1996, Massachusetts Medical Society.