Relationship of calbindin D28K-immunoreactive cells and neuropathological changes in the hippocampal formation of Alzheimer's disease
Relationship of calbindin D28K-immunoreactive cells and neuropathological changes in the hippocampal formation of Alzheimer's disease
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DOI：
10.1046/j.1440-1789.2001.00393.x
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发表时间：
2001-09-01
期刊：
影响因子：
2.3
通讯作者：
Emson, PC
中科院分区：
文献类型：
--
作者：
Iritani, S;Niizato, K;Emson, PC
以往的研究表明，钙结合蛋白在调节细胞内离子浓度方面具有重要作用，可能影响神经元在神经退行性疾病中的脆弱性。已经观察到，含有钙结合蛋白D28 K（CB）的神经元在某些情况下可能对兴奋性毒性和缺血性损伤更具抗性。在本研究中，含有CB的海马神经元发展NFT的易感性进行了研究，CB细胞的分布与阿尔茨海默病（AD）脑海马斑块密度进行了比较。有趣的是，CB阳性海马神经元不包含缠结，并且可以在退化的tau阳性锥体细胞旁边看到。海马斑块分布与CB神经元的比较表明，在一般CB阳性神经元被发现在低斑块负荷的地区。进一步比较不同程度的严重程度的情况下，CB阳性神经元相对保存的情况下，中度斑块和缠结内容，但在严重的情况下，CB阳性锥体细胞丢失。这些发现表明，CB细胞可能在疾病的早期阶段受到保护，但这种抵抗能力在AD的晚期阶段丧失。CB阳性锥体细胞不积累NFT的观察结果表明，CB阴性和CB阳性细胞中tau蛋白的水解不同。
Previous studies have reported that calcium binding proteins, which have important functions in regulating the intracellular ion concentration, may influence the vulnerability of neurons in neurodegenerative disease. It has been observed that the neurons containing calbindin D28K (CB) may in certain circumstances be more resistant to excitotoxic and ischemic injury. In the present study the susceptibility of hippocampal neurons containing CB to develop NFT was studied, and the distribution of CB cells was compared with hippocampal plaque density in the Alzheimer's disease (AD) brain. Interestingly CB-positive hippocampal neurons did not contain tangles and could be seen next to degenerating tau-positive pyramidal cells. Comparison of the hippocampal plaque distribution with that of CB neurons showed that in general CB-positive neurons were found in areas with a low plaque burden. Further comparison of cases with differing degrees of severity indicated that CB-positive neurons were relatively preserved in cases with moderate plaque and tangle content but that in severe cases the CB-positive pyramidal cells were lost. These findings indicate that CB cells may be protected in the earlier stages of the disease but that this resistance ability is lost in the late stages of AD. The observation that CB-positive pyramidal cells do not accumulate NFT suggests that proteolysis of tau differs in CB-negative and CB-positive cells.