IMMUNOREACTIVE EPIDERMAL GROWTH-FACTOR RECEPTORS IN NEURITIC PLAQUES FROM PATIENTS WITH ALZHEIMERS-DISEASE
IMMUNOREACTIVE EPIDERMAL GROWTH-FACTOR RECEPTORS IN NEURITIC PLAQUES FROM PATIENTS WITH ALZHEIMERS-DISEASE
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DOI：
10.1097/00005072-198809000-00006
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发表时间：
1988-09-01
影响因子：
3.2
通讯作者：
NANNEY, LB
中科院分区：
文献类型：
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作者：
BIRECREE, E;WHETSELL, WO;NANNEY, LB
阿尔茨海默病（AD）的神经病理学特征是大脑皮质和海马中存在神经炎性斑块（NP），以及神经元内神经纤维缠结和颗粒空泡变性。斑块形成的病因仍不清楚，但形态学NP已知含有被星形胶质细胞和变性神经元包围的淀粉样蛋白核心。虽然生长因子在损伤后的生长、分化和再生中起重要作用，但缺乏与生长因子相关的研究。表皮生长因子（Epidermal growth factor，EGF）通过与其特异性受体EGF-R相互作用，在中枢神经系统外发挥重要作用。使用抗体EGF-R（三步免疫过氧化物酶染色）结合荧光染色，我们发现，大多数NP从病理证实的AD患者以及那些少数NP在正常老化的大脑表现出强烈的EGF-R免疫反应。在斑块周围可见特异性染色，但在中央淀粉样蛋白核心中未观察到特异性染色。AD病例的组织切片也与胶质细胞酸性蛋白（GFAP）和成对螺旋丝（PHF）的抗体反应，试图确定哪种NP组分与EGF-R反应。PHF抗体在NP的外周密集染色，但在大多数NP的中央核心不染色。GFAP的抗体染色的一些反应性星形胶质细胞，毗邻斑块中只有一小部分的所有斑块。我们的结论是，神经元及其过程，但不完全可能是EGF-R免疫反应的网站。中枢神经系统内的EGF/EGF-R系统可能在响应神经元损伤和死亡的瘢痕形成中起重要作用，或者它可能在轴突或树突发芽中起重要的营养因子的作用。EGF也可能是中枢神经系统中的神经递质/神经调质。
Alzheimer''s disease (AD) is characterized neuropathologically by the presence of neuritic plaques (NP) in cerebral cortex and hippocampus, as well as intraneuronal neurofibrillary tangles and granulovacuolar degeneration. The etiology of plaque formation has remained obscure, but morphologically NP are known to contain amyloid cores surrounded by astrocytes and degenerating neurons. Although growth factors are important in growth, differentiation and regrowth in response to injury, studies relating growth factors to AD have been lacking. Epidermal growth factor (EGF) plays an important role outside the central nervous system (CNS) through interaction with its specific receptor, EGF-R. Using an antibody to EGF-R (three-step immunoperoxidase staining) in conjunction with fluorescence staining, we found that the majority of NP from patients with pathologically confirmed AD as well as those few NP in the normal aging brain showed intense EGF-R immunoreactivity. Specific staining was seen at the periphery of plaques but not in the central amyloid core. Tissue sections from AD cases were also reacted with antibodies to both glial fibrillary acidic protein (GFAP) and paired helical filaments (PHF) in an attempt to identify which component of the NP was reactive for EGF-R. The antibody to PHF densely stained the periphery of NP but not the central core in a majority of NP. The antibody to GFAP stained a few reactive astrocytes that bordered plaques in only a small proportion of all plaques present. We conclude that the neuron and its processes although not exclusively may be the site of EGF-R immunoreactivity. An EGF/EGF-R system within the CNS may play an important part in scar formation in response to neuronal injury and death or it may function as a trophic factor important in axonal or dendritic sprouting. It is also possible that EGF could serve as a neurotransmitter/neuromodulator in the CNS.