Distribution of precursor amyloid-beta-protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques.-猫眼课题宝

前体淀粉样β蛋白信使RNA在人大脑皮层中的分布：与神经原纤维缠结和神经炎斑块的关系。

DOI：

10.1073/pnas.85.5.1691

发表时间：

1988

期刊：

Proceedings of the National Academy of Sciences of the United States of America

影响因子：

11.1

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Lewis,DA;Higgins,GA;Young,WG;Goldgaber,D;Gajdusek,DC;Wilson,MC;Morrison,JH

神经原纤维缠结（NFT）和神经炎斑（NP）是阿尔茨海默病的两种神经病理学标志物，可能都含有源自人类β淀粉样蛋白的肽片段。然而，NFT 和 NP 之间关系的性质以及两者中发现的淀粉样β蛋白的来源仍不清楚。我们使用原位杂交技术绘制了三名无已知神经系统疾病的受试者和五名患有阿尔茨海默病的患者大脑新皮质中前体淀粉样蛋白 β 蛋白 mRNA 的解剖分布图。在对照受试者的大脑中，阳性杂交神经元存在于阿尔茨海默病中含有高密度神经病理学标记的皮质区域和层中，以及含有 NP 但很少有 NFT 的位点中。对上额皮质第 III 层和第 V 层内原位杂交模式的定量分析表明，与对照组和 NFT 很少的阿尔茨海默病大脑相比，阿尔茨海默病大脑中存在大量 NFT 与正杂交神经元数量减少相关。相反，未发现 NP 和含有前体淀粉样蛋白 β 蛋白 mRNA 转录物的神经元的密度之间存在相关性。这些发现表明，前体淀粉样蛋白 β 蛋白 mRNA 的表达可能是 NFT 形成所必需的，但显然不是充分的先决条件。此外，这些结果可能表明，存在于给定区域或皮层层的 NP 中的淀粉样β蛋白并非源自表达前体蛋白 mRNA 的常驻神经元细胞体。

Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid beta protein. However, the nature of the relationship between NFT and NP and the source of the amyloid beta proteins found in each have remained unclear. We used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-beta-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. In contrast, no correlation was found between the densities of NP and neurons containing precursor amyloid-beta-protein mRNA transcripts. These findings suggest that the expression of precursor amyloid-beta-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, these results may indicate that the amyloid beta protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein.