Synaptic proteins in Alzheimer's disease
Synaptic proteins in Alzheimer's disease
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DOI：
10.1385/jmn:18:1-2:53
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发表时间：
2002-02-01
影响因子：
3.1
通讯作者：
Humpel, C
中科院分区：
文献类型：
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作者：
Marksteiner, J;Kaufmann, WA;Humpel, C
嗜铬粒蛋白 A、嗜铬粒蛋白 B 和分泌粒蛋白 II 是酸性蛋白质，储存在神经元大而致密的核心囊泡中。使用针对嗜铬粒蛋白 B 分子中存在的合成肽 (PE-11) 产生的抗血清，以及针对分泌粒蛋白 II 序列中所含的分泌神经素产生的抗血清，将这些肽与嗜铬粒蛋白 A 一起定位在人海马结构中。研究了这些肽在阿尔茨海默病中的分布，并与对照受试者进行了比较。嗜铬粒蛋白 A、嗜铬粒蛋白 13 和分泌粒蛋白 II 分布明显，且分布模式有重叠。它们仅在神经元结构中检测到。嗜铬粒蛋白 B 的免疫反应密度最高。层特异性分布在齿状回的内分子层尤其明显，因为类分泌神经素的免疫反应性仅限于其最内层，而嗜铬粒蛋白 B 的免疫反应性高度集中在整个内分子层。在阿尔茨海默病中，约 10% 至 20% 的淀粉样蛋白免疫反应斑块含有嗜铬粒蛋白 A、嗜铬粒蛋白 B 或嗜铬粒蛋白 B。分泌神经氨酸。齿状回内分子层、CA1 区、下托以及内嗅皮质的 II、III 和 V 层中，分泌神经素和嗜铬粒蛋白 B 样免疫反应性的密度显着降低。本研究表明，嗜铬粒蛋白肽是人类海马通路的标志物。它们特别适合研究终止于齿状回内分子层的神经纤维。嗜铬粒蛋白肽有可能作为阿尔茨海默氏病突触变性的神经元标记物。
Chromogranin A, chromogranin B, and secretogranin II are acidic proteins which are stored in large dense core vesicles of neurons. An antiserum, raised against a synthetic peptide (PE-11), present in the chromogranin B molecule, and an antiserum raised against secretoneurin contained in the secretogranin II sequence, was used to localize these peptides together with chromogranin A in the human hippocampal formation. The distribution of these peptides was investigated in Alzheimer's disease and compared to control subjects.Chromogranin A, chromogranin 13, and secretogranin II are distinctly distributed with an overlap in their distribution patterns. They were only detected in neuronal structures. The highest density of immunoreactivity was found for chromogranin B. A layer specific distribution was especially obvious in the inner molecular layer of the dentate gyrus as secretoneurin-like immunoreactivity was restricted to its innermost part whereas that of chromogranin B was highly concentrated throughout the inner molecular layer.In Alzheimer's disease, about 10 to 20% of the amyloid-immunoreactive plaques contained either chromogranin A, chromogranin B or secretoneurin. The density of secretoneurin-and chromogranin B-like immunoreactivity was significantly reduced in the inner molecular layer of the dentate gyrus, the CA1 area, the subiculum and in layers II, III and V of the entorhinal cortex.The present study demonstrates that chromogranin peptides are markers for human hippocampal pathways. They are particularly suitable to study nerve fibers, terminating at the inner molecular layer of the dentate gyrus. Chromogranin peptides have a potential as neuronal markers for synaptic degeneration in Alzheimer's disease.