A comparison of immunohistochemical and silver staining methods for the detection of diffuse plaques in the aged canine brain

A comparison of immunohistochemical and silver staining methods for the detection of diffuse plaques in the aged canine brain
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DOI:
10.1016/j.neurobiolaging.2005.02.017
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发表时间:
2006-02-01
影响因子:
4.2
通讯作者:
Baumgärtner, W
Baumgärtner, W
中科院分区:
医学2区
文献类型:
--
作者:
Czasch, S;Paul, S;Baumgärtner, W

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斑块和淀粉样血管病变是衰老犬脑中常见的发现,而神经炎(老年性)斑块和神经原纤维缠结,这是人类阿尔茨海默病的标志,在这个物种中很少被描述。大多数关于犬年龄相关性中枢神经系统变化的研究都使用了改良的(mod.)Bielschowsky方法。因此,所获得的结果是否代表特定物种的年龄相关变化,还是由于使用了不适当的方法,仍有待确定。因此,这项研究的目的是比较各种方法在检测犬中枢神经系统中与年龄相关的变化方面的有效性。在一项初步研究中,使用针对β-淀粉样肽的单抗,对1个月至18岁的130只狗的大脑进行了A-β蛋白的筛选。用免疫组织化学和Campbell-Switzer法、Reusche法、Gallyas法、改良(mod.)法等银染方法对130只10~18岁老年犬的脑进行了比较研究。Bielschowsky和mod.博迪亚以及刚果的红色污点。血管淀粉样血管病变、斑块和海马齿状回中的A-β蛋白沉积是一个年龄依赖性过程,从8岁开始,并随着年龄的增加呈线性增加。相比之下,老年狗的斑块密度没有以类似的与年龄相关的方式上升。此外,在老年人群中还观察到了个体差异。免疫组织学是检测弥漫性斑块和淀粉样血管病变最敏感的方法,其次是Campbell-Switzer法。明尼苏达州瑞士奇Bielschowsky,和mod.波迪亚技法。任何方法均未发现神经原纤维缠结和刚果红阳性神经炎斑块。免疫组织化学检测到两种类型的斑块,它们都类似于弥漫性的人类斑块,发生在皮质浅层或深层。聚类分析表明,LIS老年犬存在低、中、高斑块数三个亚组。综上所述,斑块的检测强烈依赖于所用的方法,老化的犬脑表现为弥漫性斑块和淀粉样血管病变,但缺乏神经原纤维缠结和经典/神经炎和刚果红阳性斑块。聚类分析表明,遗传因素可能是犬弥漫性斑块形成的重要易感因素。观察到的发现证实了先前的观察,即在没有其他阿尔茨海默病特征病变的情况下,犬脑是研究弥漫性斑块和淀粉样血管病变发病机制的重要模型。(C)2005 Elsevier Inc.保留所有权利。
Plaques and amyloid angiopathy represent frequent findings in the aging canine brain, whereas neuritic (senile) plaques and neurofibrillary tangles, the hallmark of Alzheimer's disease in humans, have only rarely been described in this species. Most Studies on canine age-related CNS changes have used the modified (mod.) Bielschowsky method. Therefore, it remains to be determined, whether results obtained represent species-specific age-related changes Or are due to (lie use of inappropriate methods. Consequently, the aim of this Study was to compare the Usefulness of various methods tor the detection of age-related changes, in the canine CNS. In a preliminary study, 130 brains from dogs between 1 month and 18 years of age were screened for the presence of A-beta protein using a monoclonal antibody against the beta-amyloid peptide. Thereafter, 30 brains of aged dogs, 10-18 years of age, Out of the 130, were comparatively investigated by immunohistochemistry and silver stains Such as the method of Campbell-Switzer, Reusche, Gallyas, modified (mod.) Bielschowsky and mod. Bodian as well as the Congo red-stain. Vascular amyloid angiopathy, plaques and A-beta protein deposits in the hippocampus/dentate gyrus were an age-dependent process starting at the age of 8 years and increased in it linear fashion with age. In contrast, plaque density did not rise in a similar age-related fashion in aged dogs. Moreover, oreat individual variation,,; were observed in aged aninials. Ininiunohistology was by f"ar the most sensitive method for detection of diffuse plaques and amyloid angiopathy, followed by the Campbell-Switzer. Reusche, mod. Bielschowsky, and mod. Bodian technique. Neurofibrillary tangles and Congo red positive neuritic plaques were not found with any method. Immunohistochemically, two plaque types, both resembling diffuse human plaques, occurring in the superficial or deep cortical layers, were detected. Cluster analysis suggested the presence of three subgroups Such Lis aged dogs with it low, medium and high number of plaques. Summarized, detection of plaques depends strongly upon the method used and the aging canine brain displays diffuse plaques and amyloid angiopathy but lacks neurofibrillary tangles and classic/neuritie and Congo red positive plaques. Cluster analysis indicated, that genetic factors might be important as predisposition for the development of diffuse plaques in dogs. The observed findings substantiate previous observations, that the canine brain represents an important model to study the pathogenesis Of diffuse plaques and amyloid angiopathy in the absence of other Alzheimer disease characteristic lesions. (C) 2005 Elsevier Inc. All rights reserved.