Schmidt M L, Lee V M, Forman M, Chiu T S, Trojanowski J Q
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
Am J Pathol. 1997 Jul;151(1):69-80.
Here we describe the initial characterization of a 100-kd protein recognized by four new monoclonal antibodies that reveal abundant and unique plaque-like lesions throughout gray matter of Alzheimer's disease brains. This 100-kd protein and these new plaque-like lesions were identified by four monoclonal antibodies raised to immunogens extracted from Alzheimer's disease neurofibrillary abnormalities. However, these antibodies did not recognize hyperphosphorylated tau in Western blots or neurofibrillary lesions by immunohistochemistry. As all of these antibodies displayed similar properties, one, AMY117, was used to characterize the new plaque-like lesions in detail. These studies demonstrated that AMY117-positive plaques were not visualized by amyloid stains and never co-localized with A beta deposits, although AMY117-positive and A beta-positive lesions frequently occurred in the same cortical and subcortical gray matter regions. Abundant AMY117-positive plaques were found in the brains of all 32 sporadic Alzheimer's disease patients and all 6 elderly Down's syndrome subjects. Although AMY117-positive plaques also were seen in the brains of nondemented patients with numerous A beta deposits. AMY117-positive plaques were rare or absent in the brains of other elderly controls and patients with other neurodegenerative or neuropsychiatric disorders. We conclude that the AMY117-positive plaques described here for the first time are major lesions of the Alzheimer's disease brain. Thus, it will be important to elucidate the role played by the 100-kd protein and the AMY117 plaques in the etiology and pathogenesis of Alzheimer's disease.
在此，我们描述了一种100kd蛋白质的初步特征，该蛋白质可被四种新的单克隆抗体识别，这些抗体揭示了阿尔茨海默病大脑灰质中大量且独特的斑块样病变。这种100kd蛋白质和这些新的斑块样病变是通过针对从阿尔茨海默病神经原纤维异常中提取的免疫原产生的四种单克隆抗体鉴定出来的。然而，这些抗体在蛋白质免疫印迹中无法识别过度磷酸化的tau蛋白，在免疫组织化学中也无法识别神经原纤维病变。由于所有这些抗体都表现出相似的特性，因此选择其中一种AMY117来详细表征这些新的斑块样病变。这些研究表明，尽管AMY117阳性和Aβ阳性病变经常出现在相同的皮质和皮质下灰质区域，但AMY117阳性斑块在淀粉样蛋白染色中不可见，且从不与Aβ沉积物共定位。在所有32例散发性阿尔茨海默病患者和所有6例老年唐氏综合征患者的大脑中均发现了大量的AMY117阳性斑块。尽管在有大量Aβ沉积物的非痴呆患者的大脑中也可见到AMY117阳性斑块，但在其他老年对照以及患有其他神经退行性或神经精神疾病的患者大脑中，AMY117阳性斑块很少见或不存在。我们得出结论，此处首次描述的AMY117阳性斑块是阿尔茨海默病大脑的主要病变。因此，阐明这种100kd蛋白质和AMY117斑块在阿尔茨海默病病因学和发病机制中所起的作用将非常重要。
