MONOCLONAL ANTIBODIES RAISED AGAINST SENILE PLAQUES AND NEUROFIBRILLARY TANGLES IN ALZHEIMER'S DISEASE

阿尔茨海默病(AD)脑内不同形态的淀粉样蛋白沉积和神经原纤维缠结(NFT)是其主要的神经病理特征。1)建立了12株抗脑淀粉样蛋白的单抗。识别的抗原被确定为Abeta、C3和C4。我们用蛋白质化学方法鉴定了4个mcAb和2个mcAb分别是apoE和SP-40，40。2)建立了22株抗PHF单抗。反应性抗原为tau蛋白、神经细丝和泛素。3)利用这些mcAb，免疫组织化学研究表明，几乎所有研究的淀粉样蛋白沉积中都发现了apoE，并且apoE过度产生的星形胶质细胞和斑块之间存在空间关系。竞争ELISA法和Western印迹结合溶栓分析表明，4株mcAb可识别apoE氨基末端结构域22 kDa内的表位，在淀粉样蛋白沉积中至少存在两个不同的表位。SP-40，40存在于不同形态的Abeta沉积中，在AD和SDAT影响的脑内，星形胶质细胞也位于这些沉积附近。这些研究表明，apoE和SP-40，40表达和处理的机制可能是AD发病机制中的一个重要问题。

Cerebral amyloid deposits of varying morphology, and neurofibrillary tangles (NFT) are major neuropathological characteristics in Alzheimer's disease (AD) affected brains.1) Twelve monoclonal antibodies (mcAb's) against cerebral amyloid were established. The antigens recognized were determined to be Abeta, C3, and C4. we characterized proteinchemically the antigen four mcAb's and two mcAb's recognized to be apoE and SP-40,40. The antigens recognized with Two mcAb's remained unidentified.2) Twenty two mcAb's against PHF were established. The reactive antigens were tau protein, neurofilaments, and ubiquitin. The antigens which the rest of mcAb's e recognized were unidentified.3) Using these mcAb's, immunohistochemical study showed that apoE was found in almost all amyloid depositions studied, and that there was a spatial relation between apoE overproducing astrocytes and plaques. NFT were stained with polyclonal apoE Ab, but not with our mcAb's. Competitive ELISA and Western blot analysis combined with thrombolytic digestion of apoE indicated that our four mcAb's recognized the epitopes within 22 kDa amino-terminal domain of apoE,and there were at least two distinct epitopes of the amino-terminal domain in amyloid depositions. SP-40,40 is present in various morphologies of Abeta depositions to a lessor degree and in astrocytes which are also located close to these depositions in brains affected by AD,and SDAT.These studies suggest that the mechanisms underlying the expression and processing of apoE,and SP-40,40 may be an essential issue in the pathogenesis of AD.