Head E, Moffat K, Das P, Sarsoza F, Poon W W, Landsberg G, Cotman Carl W, Murphy M P
Department of Neurology, Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA.
Neurobiol Aging. 2005 May;26(5):749-63. doi: 10.1016/j.neurobiolaging.2004.06.015.
The current study describes both Abeta and tau abnormalities that accumulate in the brains of aged (16-21 years), but not young (<4 years) clinically characterized cats. Diffuse plaques that were morphologically different from what is typically observed in the human brain could be detected with 4G8 (Abeta17-24) or an Abeta1-42-specific antibody but not with N-terminal Abeta or an Abeta1-40-specific antibody. SELDI-TOF mass spectrometry experiments indicated that cat brain Abeta consisted almost entirely of Abeta1-42. Markers of tau hyperphosphorylation (AT8 and PHF-1) labeled a subset of neurons in two aged animals. In the hilus of the hippocampus, a subset of AT8 positive neurons showed a sprouting morphology similar to that observed in human brain. Western blot analysis with antibodies against hyperphosphorylated tau indicated that tau is hyperphosphorylated in the aged cat and contains many of the same epitopes found in Alzheimer's disease (AD) brain. Thus, the aged cat brain develops AD-related lesions with important morphological and biochemical differences compared to human brain.
当前研究描述了在临床特征为老年（16 - 21岁）而非幼年（<4岁）的猫脑中积累的β淀粉样蛋白（Abeta）和tau蛋白异常情况。用4G8（Abeta17 - 24）或Abeta1 - 42特异性抗体可检测到形态上与人类大脑中通常观察到的不同的弥漫性斑块，但用N端Abeta或Abeta1 - 40特异性抗体则检测不到。表面增强激光解吸电离飞行时间质谱（SELDI - TOF）实验表明，猫脑Abeta几乎完全由Abeta1 - 42组成。tau蛋白过度磷酸化的标志物（AT8和PHF - 1）在两只老年动物的一部分神经元中标记阳性。在海马体门区，一部分AT8阳性神经元呈现出与人类大脑中观察到的相似的发芽形态。用针对过度磷酸化tau蛋白的抗体进行的蛋白质印迹分析表明，老年猫脑中的tau蛋白发生了过度磷酸化，并且含有许多与阿尔茨海默病（AD）脑中共有的表位。因此，老年猫脑会出现与AD相关的病变，与人类大脑相比存在重要的形态学和生物化学差异。
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