Age-related changes of Alzheimer's disease-associated proteins in cynomolgus monkey brains
Age-related changes of Alzheimer's disease-associated proteins in cynomolgus monkey brains
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DOI：
10.1016/j.bbrc.2003.09.012
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发表时间：
2003-10-17
影响因子：
3.1
通讯作者：
Yoshikawa, Y
中科院分区：
文献类型：
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作者：
Kimura, N;Tanemura, K;Yoshikawa, Y
我们的特点老年斑（SP）在食蟹猴脑中的化学，也检查了与年龄相关的生化变化阿尔茨海默病（AD）相关的蛋白质在这些大脑从不同年龄的猴子。在老年猴（>20岁）的新皮层中，我们发现SP，但没有神经元缠结（NFT）。针对β-淀粉样前体蛋白（APP）或载脂蛋白E（ApoE）的抗体染色SP;然而，两种抗原的免疫染色模式不同。APP只存在于肿胀的神经突起，但ApoE存在于整个SP的所有部分。Western blot分析显示，APP的表达模式随着年龄的增长而变化。尽管全长APP 695蛋白主要在年轻猴（4岁）的脑中表达，但全长APP 751蛋白在老年猴（>20岁）的脑中表达增加。生化分析还表明，各种AD相关蛋白的水平随年龄的神经末梢分数显着增加。随着年龄的增长，SP相关（APP）和NFT相关蛋白（tau，活化糖原合成酶激酶3 β，细胞周期蛋白依赖性激酶5，p35和p25）在神经末梢部分中积累;然而，我们在老年食蟹猴大脑中没有发现NFT或配对的tau螺旋丝。这种与年龄相关的积累，这些蛋白质的神经末梢部分是类似的，在我们的实验室以前观察到的早老素-1（PS-1）。这些SP相关蛋白在这一部分的积累可能是一个因果关系的自发形成SP的事件，因此，SP可能最初在神经末梢形成。两者合计，这些结果表明，深入调查与年龄相关的神经末梢和轴突运输的变化将有助于更好地了解神经退行性疾病，如AD的发病机制。(C)2003年爱思唯尔公司All rights reserved.
We characterized senile plaques (SPs) immunohistochemically in cynomolgus monkey brains and also examined age-related biochemical changes of Alzheimer's disease (AD)-associated proteins in these brains from monkeys of various ages. In the neocortex of aged monkeys (>20 years old), we found SPs but no neurofibrillary tangles (NFTs). Antibodies against beta-amyloid precursor protein (APP) or apolipoprotein E (ApoE) stained SPs; however, the pattern of immunostaining was different for the two antigens. APP was present only in swollen neurites, but ApoE was present throughout all parts of SPs. Western blot analysis revealed that the pattern of APP expression changed with age. Although full-length APP695 protein was mainly expressed in brains from young monkeys (4 years old), the expression of full-length APP751 protein was increased in brains from older monkeys (>20 years old). Biochemical analyses also showed that levels of various AD-associated proteins increased significantly with age in nerve ending fractions. Both SP-associated (APP) and NFT-associated proteins (tau, activated glycogen synthase kinase 3beta, cyclin dependent kinase 5, p35, and p25) accumulated in the nerve ending fraction with increasing age; however, we found no NFTs or paired helical filaments of tau in aged cynomolgus monkey brains. This age-related accumulation of these proteins in the nerve ending fraction was similar to that observed in our laboratory previously for presenilin-1 (PS-1). The accumulation of these SP-associated proteins in this fraction may be a causal event in the spontaneous formation of SPs; thus, SPs may be formed initially in nerve endings. Taken together, these results suggest that intensive investigation of age-related changes in the nerve ending and in axonal transport will contribute to a better understanding of the pathogenesis of neurodegenerative disorders such as AD. (C) 2003 Elsevier Inc. All rights reserved.