Lambert J-C, Mann D, Richard F, Tian J, Shi J, Thaker U, Merrot S, Harris J, Frigard B, Iwatsubo T, Lendon C, Amouyel P
Unité INSERM 508, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59019 Lille cédex, France.
J Neurol Neurosurg Psychiatry. 2005 Jul;76(7):928-33. doi: 10.1136/jnnp.2004.048983.
It has been proposed that, independent of the epsilon4 allele, APOE promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for Alzheimer's disease by modulating APOE expression.
To measure the level of APOE expression in Alzheimer's disease.
Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer's disease in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes.
An inverse correlation between APOE expression level and A beta loads was observed. As previously described and extended to 114 cases here, an association between the -219 TT genotype and a higher level of parenchymal A beta deposition was found, irrespective of APOE epsilon4 allele status. This effect was more pronounced in older individuals, whereas higher A beta load appeared more closely related to epsilon4 in the younger age group (cut off point at the median age at death (72.5 years)). The -219 TT genotype was associated with a decrease in APOE expression. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p = 0.01).
In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T polymorphism, may influence risk and constitute a determinant A beta load in Alzheimer's disease.
有人提出，载脂蛋白E（APOE）启动子多态性（-491 A/T和-219 G/T）可能独立于ε4等位基因，通过调节APOE表达成为阿尔茨海默病的危险因素。
测量阿尔茨海默病中APOE的表达水平。
1986年至2001年期间，从英国大曼彻斯特地区114例早发和晚发散发性阿尔茨海默病患者尸检中获取大脑。从84个大脑中提取总RNA。从法国里尔16例疑似阿尔茨海默病患者的新鲜血液中获取纯化淋巴细胞。通过逆转录聚合酶链反应测定大脑和淋巴细胞中APOE及β-肌动蛋白基因的表达。
观察到APOE表达水平与β淀粉样蛋白（Aβ）负荷呈负相关。如先前所述并在此扩展至114例病例，发现-219 TT基因型与实质Aβ沉积水平较高有关，与APOE ε4等位基因状态无关。这种效应在老年人中更明显，而在较年轻年龄组（以死亡年龄中位数（72.5岁）为分界点）中，较高的Aβ负荷似乎与ε4更为密切相关。-219 TT基因型与APOE表达降低有关。疑似阿尔茨海默病病例的淋巴细胞中APOE表达较对照组降低60%（p = 0.01）。
在年龄最大的个体中，部分由-219 G/T多态性调节的APOE表达降低可能影响患病风险，并构成阿尔茨海默病中Aβ负荷的一个决定因素。
