Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer's disease
Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer's disease
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DOI：
10.1196/annals.1379.003
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Gan, Wen-Biao
中科院分区：
文献类型：
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作者：
Grutzendler, Jaime;Helmin, Kathryn;Gan, Wen-Biao
营养不良的神经突与阿尔茨海默病（AD）的纤维状淀粉样蛋白沉积有关，但淀粉样蛋白沉积附近突触结构变化的频率和类型尚未得到很好的表征。利用高分辨率共聚焦显微镜对亲脂性染料标记的树突和硫黄素- s标记的淀粉样斑块进行成像，我们系统地分析了转基因AD小鼠模型（papp）和人类死后大脑中与淀粉样蛋白沉积相关的树突结构变化。我们发现，在papp小鼠中，通过淀粉样蛋白沉积物或距离淀粉样蛋白沉积物40 μ m范围内的树突分支表现出各种树突异常，如树突棘丢失、轴萎缩、弯曲、分枝突然终止、静脉曲张形成和发芽。在死后的人类AD组织中也发现了类似的树突结构改变，脊柱丢失是papp小鼠和人类AD大脑中最常见的异常。这些结果表明，纤维状淀粉样蛋白沉积物及其周围的微环境对树突有毒，并可能导致AD患者神经元回路的显著破坏。
Dystrophic neurites are associated with fibrillar amyloid deposition in Alzheimer's disease (AD), but the frequency and types of changes in synaptic structures near amyloid deposits have not been well characterized. Using high-resolution confocal microscopy to image lipophilic dye-labeled dendrites and thioflavin-S-labeled amyloid plaques, we systematically analyzed the structural changes of dendrites associated with amyloid deposition in both a transgenic mouse model of AD (PSAPP) and in human postmortem brain. We found that in PSAPP mice, dendritic branches passing through or within 40 mu m from amyloid deposits displayed various dendritic abnormalities such as loss of dendritic spines, shaft atrophy, bending, abrupt branch endings, varicosity formation, and sprouting. Similar structural alterations of dendrites were seen in postmortem human AD tissue, with spine loss as the most common abnormality in both PSAPP mice and human AD brains. These results demonstrate that fibrillar amyloid deposits and their surrounding microenvironment are toxic to dendrites and likely contribute to significant disruption of neuronal circuits in AD.