Liao A, Gómez-Isla T, Clatworthy A, Hyman B T
Alzheimer's Research, Department of Neurology, Massachusetts General Hospital-East, 149 13th Street, Charlestown, MA 02129, USA.
Brain Res. 1999 Jan 23;816(2):295-8. doi: 10.1016/s0006-8993(98)01005-1.
Over 45 mutations within the coding region of presenilin-1 (PS-1) are associated with an autosomal dominant form of Alzheimer's disease. Recently allele 1 of a polymorphism within intron-8 was reported to be in disequilibrium with Alzheimer's disease in a group of patients with sporadic Alzheimer's disease. This association has been replicated in some, but not all, studies. To determine whether the PS-1 intronic polymorphism is overrepresented in Alzheimer's disease in an autopsy-proven series, and to examine whether allele 1 is associated with a specific neuropathological phenotype, polymerase chain reaction based technique was used to assess the genotype in 85 cases of Alzheimer's disease. The resulting genotypes were compared with age of onset, duration of illness, and quantitative neuropathological measures of Abeta(total), Abeta(1-40), Abeta(1-42), neurofibrillary tangle number and neuron number. The 1/1 genotype did not associate with any differences in the clinical or neuropathological phenotype. These data suggest that the PS-1 intron-8 polymorphism does not strongly impact the clinical or neuropathologic features of Alzheimer's disease.
早老素-1（PS-1）编码区内超过45种突变与常染色体显性遗传形式的阿尔茨海默病相关。最近，有报道称在一组散发性阿尔茨海默病患者中，内含子8内一种多态性的等位基因1与阿尔茨海默病存在不平衡状态。这种关联在一些研究中得到了重复，但并非所有研究都如此。为了确定在经尸检证实的系列中，PS-1内含子多态性在阿尔茨海默病中是否过度存在，并检查等位基因1是否与特定的神经病理表型相关，采用基于聚合酶链反应的技术对85例阿尔茨海默病患者的基因型进行了评估。将所得基因型与发病年龄、病程以及β淀粉样蛋白（总）、β淀粉样蛋白（1-40）、β淀粉样蛋白（1-42）、神经原纤维缠结数量和神经元数量的定量神经病理测量结果进行了比较。1/1基因型与临床或神经病理表型的任何差异均无关联。这些数据表明，PS-1内含子8多态性对阿尔茨海默病的临床或神经病理特征没有强烈影响。
