AGGREGATION OF THE AMYLOID PRECURSOR PROTEIN WITHIN DEGENERATING NEURONS AND DYSTROPHIC NEURITES IN ALZHEIMERS-DISEASE
AGGREGATION OF THE AMYLOID PRECURSOR PROTEIN WITHIN DEGENERATING NEURONS AND DYSTROPHIC NEURITES IN ALZHEIMERS-DISEASE
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DOI：
10.1016/0306-4522(92)90265-4
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发表时间：
1992-06-01
期刊：
影响因子：
3.3
通讯作者：
COTMAN, CW
中科院分区：
文献类型：
--
作者：
CUMMINGS, BJ;SU, JH;COTMAN, CW
使用一种针对纯化的、天然的人蛋白酶连接蛋白2/淀粉样前体蛋白的单克隆抗体，该抗体识别淀粉样前体蛋白的氨基末端表位，并检测淀粉样前体蛋白的所有主要亚型，我们检测了淀粉样前体蛋白在阿尔茨海默氏症和老年对照大脑中的定位。对照脑胞浆神经元淀粉样前体蛋白染色很轻，未见神经炎染色。在阿尔茨海默氏症的大脑中，我们检测到许多淀粉样蛋白前体蛋白免疫阳性的神经元，在选择的区域有中等到强烈的染色。许多神经元还含有不同程度的淀粉样前体蛋白离散颗粒，细胞内积聚，特别是少数锥体神经元完全充满淀粉样前体蛋白颗粒。“幽灵”样淀粉样前体蛋白颗粒排列成金字塔状，斑块状。我们检测到长，淀粉样前体蛋白免疫阳性的神经突围绕并进入斑块。许多包含肿胀的静脉曲张沿其长度或结束在球茎尖端。淀粉样前体蛋白在阿尔茨海默氏症大脑中的免疫反应性主要表现为颗粒状沉积物（斑块）。淀粉样前体蛋白颗粒似乎不会在星形胶质细胞或小胶质细胞内共定位，这是由抗胶质纤维酸性蛋白和抗白细胞共同抗原抗体或蓖麻凝集素双标记免疫组织化学证明的。淀粉样蛋白前体偶尔可以在阿尔茨海默氏症患者的大脑血管中检测到。淀粉样前体蛋白免疫反应性的主要神经元和神经性定位表明，阿尔茨海默病病理中观察到的淀粉样前体蛋白的大部分是神经元来源，并提示斑块发育的时间过程，从神经元淀粉样前体蛋白积累开始，然后沉积到细胞外空间，随后由星形胶质细胞或小胶质细胞加工，最终导致斑块中β -淀粉样肽的积累。
Using a monoclonal antibody raised against purified, native, human protease nexin-2/amyloid precursor protein, which recognizes an amino terminal epitope on the amyloid precursor protein and detects all major isoforms of amyloid precursor protein, we examined the localization of the amyloid precursor protein within Alzheimer's and aged control brains. Very light cytoplasmic neuronal amyloid precursor protein staining but no neuritic staining was visible in control brains. In the Alzheimer's brain, we detected numerous amyloid precursor protein-immunopositive neurons with moderate to strong staining in select regions. Many neurons also contained varying levels of discrete granular, intracellular accumulations of amyloid precursor protein, and a few pyramidal neurons in particular appeared completely filled with amyloid precursor protein granules. "Ghost"-like deposits of amyloid precursor protein granules arranged in pyramidal, plaque-like shapes were identified. We detected long, amyloid precursor protein-immunopositive neurites surrounding and entering plaques. Many contained swollen varicosities along their length or ended in bulbous tips. Amyloid precursor protein immunoreactivity in the Alzheimer's brain was primarily present as granular deposits (plaques). The amyloid precursor protein granules do not appear to co-localize within either astrocytes or microglia, as evidenced by double-labeling immunohistochemistry with anti-glial fibrillary acidic protein and anti-leukocyte common antigen antibodies or Rinucus cummunicus agglutin lectin. Amyloid precursor protein could occasionally be detected in blood vessels in Alzheimer's brains.The predominantly neuronal and neuritic localization of amyloid precursor protein immunoreactivity indicates a neuronal source for much of the amyloid precursor protein observed in Alzheimer's disease pathology, and suggests a time-course of plaque development beginning with neuronal amyloid precursor protein accumulation, then deposition into the extracellular space, subsequent processing by astrocytes or microglia, and resulting in beta-amyloid peptide accumulation in plaques.