In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories
In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories
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DOI：
10.1093/jnen/62.2.137
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发表时间：
2003-02-01
影响因子：
3.2
通讯作者：
Hyman, BT
中科院分区：
文献类型：
--
作者：
D'Amore, JD;Kajdasz, ST;Hyman, BT
对老年斑的尸检分析揭示了其附近的许多营养不良过程。我们使用阿尔茨海默病（AD）转基因模型的体内多光子显微镜来同时对老年斑和附近的神经元过程进行成像。通过免疫荧光染色或硫黄素-S 标记斑块，并用荧光葡聚糖缀合物标记神经元突起。斑块附近的 3 维体积成像揭示了弥漫斑块内或附近神经突几何形状的细微变化。相比之下，神经突形态的破坏，包括紧邻斑块周围的营养不良的神经突以及神经突轨迹的主要改变，被发现与硫黄素-S阳性斑块相关。硫黄素-S 阳性斑块 50 微米内的所有标记过程中，近一半发生了改变，这表明相当大的神经纤维改变“光环”延伸到硫黄素-S 斑块的离散边界之外。这些结果支持了这样的假设：致密的硫黄素-S 阳性斑块会破坏 AD 中的神经纤维网。
Postmortem analyses of senile plaques reveal numerous dystrophic processes in their vicinity. We used in vivo multiphoton microscopy of a transgenic model of Alzheimer disease (AD) to simultaneously image senile plaques and nearby neuronal processes. Plaques were labeled by immunofluorescent staining or thioflavine-S and neuronal processes were labeled with a fluorescent dextran conjugate. Imaging of 3-dimensional volumes in the vicinity of plaques revealed subtle changes in neurite geometry in or near diffuse plaques. By contrast, disruptions in neurite morphology, including dystrophic neurites immediately surrounding plaques as well as major alterations in neurite trajectories, were seen in association with thioflavine-S-positive plaques. Nearly half of all labeled processes that came within 50 mum of a thioflavine-S-positive plaque were altered, suggesting a fairly large "halo" of neuropil alterations that extend beyond the discrete border of a thioflavine-S plaque. These results support the hypothesis that compact thioflavine-S-positive plaques disrupt the neuropil in AD.