Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease.

Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease.
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发表时间:
1991-09
期刊:
The American journal of pathology
影响因子:
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通讯作者:
E. Cochran;B. Bacci;Y. Chen;A. Patton;P. Gambetti;L. Autilio‐Gambetti
E. Cochran;B. Bacci;Y. Chen;A. Patton;P. Gambetti;L. Autilio‐Gambetti
中科院分区:
其他
文献类型:
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作者:
E. Cochran;B. Bacci;Y. Chen;A. Patton;P. Gambetti;L. Autilio‐Gambetti

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阿尔茨海默病(AD)的一个显著特征是存在与淀粉样前体蛋白(APP)和泛素(Ub)抗体发生免疫反应的营养不良神经突。作者检查了其他慢性疾病中存在的营养不良性轴突(DA),如家族性婴儿神经轴索营养不良(INAD)、衰老、囊性纤维化和胆道梗阻,以及持续时间较短的疾病,如人类免疫缺陷病毒(HIV)白质脑病、梗死和放射治疗,以确定APP和Ub免疫反应性是否是AD DA所特有的。大量的DA与APP的A4,C-和N-末端区域以及Ub的抗体发生免疫反应。Ub和APP免疫反应性经常但不总是共定位。“急性”DA一般反应更强烈,在大量的APP抗体比Ub,而相反的是真正的“慢性”DA。无结构DA免疫染色弥漫。在DA与核心或颗粒,Ub免疫反应偶尔限于这些结构,而与APP抗体的反应是更扩散。鉴于这一论点,即损害蛋白水解是共同的发病步骤,在DA的形成,Ub免疫反应在所有DA可能表明一个替代的尝试,通过激活的Ub系统降解积累的组件。APP在DA形成中的作用仍有待确定。
A distinctive feature of Alzheimer's disease (AD) is the presence of dystrophic neurites that immunoreact with antibodies to amyloid precursor protein (APP) and ubiquitin (Ub). The authors examined dystrophic axons (DA) present in other chronic conditions such as familial infantile neuroaxonal dystrophy (INAD), aging, cystic fibrosis, and biliary obstruction as well as in conditions of shorter duration such as human immunodeficiency virus (HIV) leucoencephalopathy, infarction and radiation therapy to determine whether APP and Ub immunoreactivity was unique to the DA of AD. A large number of DA immunoreacted with antibodies to the A4, C- and N-terminal regions of APP as well as to Ub. Ub and APP immunoreactivities often, but not always, colocalized. "Acute" DA generally reacted more intensely and in larger number with antibodies to APP than to Ub, whereas the reverse was true for "chronic" DA. Structureless DA immunostained diffusely. In DA with cores or granules, the Ub immunoreaction was occasionally limited to these structures, whereas reaction with antibodies to APP was more diffuse. In view of the contention that impairment of proteolysis is the common pathogenetic step in the formation of DA, Ub immunoreactivity in all DA may indicate a vicarious attempt to degrade accumulated components through an activation of the Ub system. The role of APP in the formation of DA remains to be determined.