Birecree E, Whetsell W O, Stoscheck C, King L E, Nanney L B
Department of Plastic Surgery, Vanderbilt University, Nashville, Tennessee.
J Neuropathol Exp Neurol. 1988 Sep;47(5):549-60. doi: 10.1097/00005072-198809000-00006.
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.
阿尔茨海默病（AD）的神经病理学特征是大脑皮层和海马中存在神经炎性斑块（NP），以及神经元内神经原纤维缠结和颗粒空泡变性。斑块形成的病因尚不清楚，但从形态学上看，已知NP含有被星形胶质细胞和变性神经元包围的淀粉样核心。尽管生长因子在生长、分化以及对损伤的再生反应中很重要，但将生长因子与AD相关联的研究却很缺乏。表皮生长因子（EGF）通过与其特异性受体EGF-R相互作用，在中枢神经系统（CNS）之外发挥重要作用。我们使用针对EGF-R的抗体（三步免疫过氧化物酶染色）并结合荧光染色，发现病理确诊为AD的患者的大多数NP以及正常衰老大脑中的少数NP均显示出强烈的EGF-R免疫反应性。在斑块周边可见特异性染色，但在中央淀粉样核心中未见。AD病例的组织切片还与针对胶质纤维酸性蛋白（GFAP）和双螺旋丝（PHF）的抗体反应，以试图确定NP的哪个成分对EGF-R有反应。针对PHF的抗体在大多数NP中密集染色NP的周边，但不染色中央核心。针对GFAP的抗体仅在所有斑块中的一小部分中染色了一些与斑块接壤的反应性星形胶质细胞。我们得出结论，神经元及其突起虽然不是唯一的，但可能是EGF-R免疫反应性的部位。中枢神经系统内的EGF/EGF-R系统可能在对神经元损伤和死亡的反应中瘢痕形成中起重要作用，或者它可能作为对轴突或树突发芽很重要的营养因子发挥作用。EGF也有可能在中枢神经系统中作为神经递质/神经调节剂起作用。
