beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine
beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine
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DOI：
10.1006/nlme.1996.0039
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发表时间：
1996-07-01
影响因子：
2.7
通讯作者：
Cotman, CW
中科院分区：
文献类型：
--
作者：
Cummings, BJ;Head, E;Cotman, CW
众所周知，β-淀粉样蛋白在阿尔茨海默病中异常堆积；然而，β-淀粉样蛋白与认知功能障碍的关系尚未明确，并且经常被神经原纤维缠结的存在所混淆。我们用犬类研究了缺乏神经原纤维缠结的衰老动物模型中β-淀粉样蛋白积聚与认知功能之间的关系。对20只犬(11只纯种比格犬和9只杂种犬)在六项认知任务中的表现进行了测量。这些任务包括奖励法和客体法学习，以及辨别、反转、物体识别和空间学习和记忆。上了年纪的狗在一些任务中受到了损害，但在另一些任务中没有。在许多年长的动物身上发现了β-淀粉样蛋白免疫阳性斑块。斑块均为弥漫性亚型，其中许多含有完整的神经元，神经细丝双重标记检测到。未检测到神经原纤维缠结。β-淀粉样蛋白还与许多神经元的突起和血管有关。利用计算机图像分析，我们量化了β-淀粉样蛋白在内嗅皮层、额叶皮质和小脑中所占的面积。控制了与年龄相关的β-淀粉样蛋白的增加，我们观察到，β-淀粉样蛋白沉积的增加与辨别学习(r=.80)、逆转学习(r=.65)和空间学习(r=.54)的缺陷密切相关，但与其他任务无关。在正文中讨论的品种之间存在一些差异。总体而言，这些数据表明，在神经纤维缠结形成之前，β-淀粉样蛋白沉积可能是与年龄相关的认知功能障碍的一个促成因素。(C)1996年学术出版社。
It is well known that beta-amyloid accumulates abnormally in Alzheimer's disease; however, beta-amyloid's relationship to cognitive dysfunction has not been clearly established and is often confounded by the presence of neurofibrillary tangles. We used canines to investigate the relationship between beta-amyloid accumulation and cognitive function in an animal model of aging lacking neurofibrillary tangles. The performance of 20 canines (11 purebred beagles and 9 mongrels) on a battery of six cognitive tasks was measured. These tasks included Reward Approach and Object Approach learning, as well as Discrimination, Reversal, Object Recognition, and Spatial learning and memory. Aged canines were impaired on some tasks but not others. beta-Amyloid-immunopositive plaques were found in many of the older animals. Plaques were all of the diffuse subtype and many contained intact neurons detected with double-labeling for neurofilaments. No neurofibrillary tangles were detected. beta-Amyloid was also associated with the processes of many neurons and with blood vessels. Using computerized image analysis, we quantified the area occupied by beta-amyloid in entorhinal cortex, frontal cortex, and cerebellum. Controlling for age-related increases in beta-amyloid, we observed that increased beta-amyloid deposition is strongly associated with deficits on Discrimination learning (r = .80), Reversal learning (r = .65), and Spatial learning (r = .54) but not the other tasks. There were a few differences between breeds which are discussed in the text. Overall, these data suggest that beta-amyloid deposition may be a contributing factor to age-related cognitive dysfunction prior to the onset of neurofibrillary tangle formation. (C) 1996 Academic Press, Inc.