Chromogranin peptides in Alzheimer's disease
Chromogranin peptides in Alzheimer's disease
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DOI：
10.1016/j.exger.2003.09.018
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Marksteiner, J
中科院分区：
文献类型：
--
作者：
Lechner, T;Adlassnig, C;Marksteiner, J
突触紊乱可能在阿尔茨海默病的病理生理学中起关键作用。为了表征阿尔茨海默病患者脑中的差异突触改变，嗜铬粒蛋白A、嗜铬粒蛋白B和分泌神经素被用作大致密核心囊泡的可溶性成分，突触素作为囊泡膜标记物，钙结合蛋白作为胞质蛋白。在对照组中，嗜铬粒蛋白B和分泌粒蛋白主要共同包含在中间神经元中，而嗜铬粒蛋白A主要存在于锥体神经元中。在阿尔茨海默病中，约30%的β-淀粉样蛋白斑块与嗜铬粒蛋白A共标记，20%与分泌神经蛋白共标记，15%与嗜铬粒蛋白B共标记。不到5%的β-淀粉样蛋白斑块分别含有突触素或钙结合蛋白。Setniquantitative免疫组化显示显着损失嗜铬粒蛋白B-和分泌神经素样免疫反应，在背外侧，内嗅，眶额皮质。嗜铬粒蛋白A表现出更复杂的变化。它是唯一的嗜铬粒蛋白肽表达的神经胶质细胞酸性蛋白含有细胞。大约40%的嗜铬粒蛋白A免疫阳性斑块和细胞外沉积物被激活的小胶质细胞包围和弥漫。嗜铬粒蛋白的不平衡可用性可能是神经传递受损和致密核心囊泡功能降低的原因。嗜铬粒蛋白A可能是阿尔茨海默病中发现的神经元、神经胶质和炎症机制之间的介质。(C)2003年爱思唯尔公司All rights reserved.
Synaptic disturbances may play a key role in the pathophysiology of Alzheimer's disease. To characterize differential synaptic alterations in the brains of Alzheimer patients, chromogranin A, chromogranin B and secretoneurin were applied as soluble constituents for large dense core vesicles, synaptophysin as a vesicle membrane marker and calbindin as a cytosolic protein.In controls, chromogranin B and secretogranin are largely co-contained in interneurons, whereas chromogranin A is mostly found in pyramidal neurons. In Alzheimer's disease, about 30% of beta-amyloid plaques co-labelled with chromogranin A, 20% with secretoneurin and 15% with chromogranin B. Less than 5% of beta-amyloid plaques contained synaptophysin or calbindin, respectively. Setniquantitative immunohistochemistry revealed a significant loss for chromogranin B- and secretoneurin-like immunoreactivity in the dorsolateral, the entorhinal, and orbitofrontal cortex. Chromogranin A displayed more complex changes. It was the only chromogranin peptide to be expressed in glial fibrillary acidic protein containing cells. About 40% of chromogranin A immunopositive plaques and extracellular deposits were surrounded and pervaded by activated microglia.The present study demonstrates a loss of presynaptic proteins involved in distinct steps of exocytosis. An imbalanced availability of chromogranins may be responsible for impaired neurotransmission and a reduced functioning of dense core vesicles. Chromogranin A is likely to be a mediator between neuronal, glial and inflammatory mechanisms found in Alzheimer disease. (C) 2003 Elsevier Inc. All rights reserved.