Increased cholesterol in Aβ-positive nerve terminals from Alzheimer's disease cortex
Increased cholesterol in Aβ-positive nerve terminals from Alzheimer's disease cortex
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DOI：
10.1016/j.neurobiolaging.2005.10.018
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Cole, Gregory M.
中科院分区：
文献类型：
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作者：
Gylys, Karen Hoppens;Fein, Jeffrey A.;Cole, Gregory M.
突触丧失在阿尔茨海默病（AD）中尚不清楚，但有证据表明这是一个关键的病理事件。为了精确检测稳定的突触变化，我们开发了流式细胞术分析从冷冻保存的阿尔茨海默病样品制备的突触体的方法，并且先前已经表明淀粉样蛋白- β (A β)在阿尔茨海默病皮层存活的突触前终末中积累。在目前的实验中，我们更详细地检查了含淀粉样蛋白的末端，首先对来自AD皮层的突触体进行了A β和一系列标记，然后使用象限分析来比较淀粉样蛋白阳性和淀粉样蛋白阴性末端。淀粉样蛋白阳性的突触体比淀粉样蛋白阴性的突触体大（p < 0.007），脂质标记物胆固醇（27%,p < 0.0005）和GM1神经节苷脂（24%,p < 0.005）的平均荧光显著增加。淀粉样蛋白末端的SNAP-25免疫荧光增加了31% (P < 0.0001)，与淀粉样蛋白积累的发芽反应一致。这些结果表明突触末端的A - β积累可能是细胞外淀粉样蛋白沉积之前或独立于细胞外淀粉样蛋白沉积的功能障碍。(c) 2005爱思唯尔公司版权所有。
Synapse loss in Alzheimer's disease (AD) is poorly understood but evidence suggests it is a key pathological event. In order to precisely detect stable synaptic changes, we have developed methods for flow cytometry analysis of synaptosomes prepared from cryopreserved AD samples, and have previously shown that amyloid-beta (A beta) accumulates in surviving presynaptic terminals in AD cortex. In the present experiments we have examined amyloid-containing terminals in more detail, first dual labeling synaptosomes from AD cortex for A beta and a series of markers, and then using quadrant analysis to compare amyloid-positive and amyloid-negative terminals. Amyloid-positive synaptosomes were larger in size than amyloid-negatives (p < 0.007), and significant increases were observed in mean fluorescence for the lipid raft markers cholesterol (27%; p < 0.0005) and GM1 ganglioside (24%; p < 0.005). SNAP-25 immunofluorescence was increased by 31% (P < 0.0001) in amyloid-bearing terminals, consistent with a sprouting response to amyloid accumulation. These results suggest that A beta accumulation in synaptic terminals may underly dysfunction prior to or independent of extracellular amyloid deposition. (c) 2005 Elsevier Inc. All rights reserved.