β-amyloid and tau pathology in the aging feline brain
β-amyloid and tau pathology in the aging feline brain
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DOI：
10.1002/cne.24741
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发表时间：
2019-07-12
影响因子：
2.5
通讯作者：
Hefti, Marco M.
中科院分区：
文献类型：
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作者：
Fiock, Kimberly L.;Smith, Jodi D.;Hefti, Marco M.
已知家猫（Felis卡图斯）发展认知障碍，并且几个小系列已经证明β-淀粉样蛋白和tau聚集，包括神经元缠结，随着年龄的增长，使它们成为阿尔茨海默病（AD）的有希望的生理模型。因此，我们报告了迄今为止最大的猫尸检队列的32只猫，年龄从1.5到22.1岁不等，根据NIA阿尔茨海默氏症协会标准进行系统的神经病理学评估。福尔马林固定石蜡包埋的脑组织切片是从爱荷华州兽医学院尸检的猫中回顾性获得的。我们发现β-淀粉样蛋白染色，主要在研究中使用的32只猫中的27只的皮质层IV和VI中，其中4只动物显示tau阳性缠结和神经纤维丝。在这些病例中，75%（3/4）的tau蛋白沉积仅限于内嗅皮质，而1例病例显示整个海马结构和新皮质弥漫性阳性染色。这最后一个病例显示出测试的所有磷酸化tau特异性抗体的阳性染色，类似于在人AD中观察到的模式。有趣的是，我们看到了比人类AD更高的pretangles与tangles的比例，并且在任何使用的染色剂上都没有病例显示神经炎斑块。我们的研究结果表明，老化的家猫自发地发展β-淀粉样蛋白和tau蛋白病理学，与人类AD中所见的相似，但不完全相同。这表明，家猫可能作为一个潜在的模型，机械和治疗AD的研究，但需要额外的研究，以确定人类和猫科动物的衰老的神经病理学之间的差异。
Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both beta-amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feline autopsy cohort to date of 32 cats ranging from 1.5 to 22.1 years of age, with systematic neuropathologic assessment according to NIA-Alzheimer's Association Criteria. Formalin-fixed paraffin-embedded tissue sections of brain were obtained retrospectively from cats autopsied at the Iowa State College of Veterinary Medicine. We found beta-amyloid staining, predominantly in Cortical Layers IV and VI in 27 of the 32 cats used in the study, with four of these animals showing tau-positive tangles and neuropil threads. In 75% of these cases (3/4), tau deposition was limited to entorhinal cortex, while one case showed diffuse positive staining throughout the hippocampal formation and neocortex. This last case showed positive staining for all phospho-tau-specific antibodies tested, similar to the pattern seen in human AD. Interestingly, we saw a higher ratio of pretangles to tangles than that in human AD, and none of the cases showed neuritic plaques on any of the stains used. Our findings indicate that aging domestic cats spontaneously develop both beta-amyloid and tau pathology similar, but not identical to that seen in human AD. This suggests that the domestic cat may serve as a potential model for mechanistic and therapeutic AD studies, but that additional research is needed to identify differences between the neuropathology of aging in humans and felines.