In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease
In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease
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DOI：
10.1073/pnas.97.13.7609
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发表时间：
2000-06-20
影响因子：
11.1
通讯作者：
Lee, VMY
中科院分区：
文献类型：
--
作者：
Skovronsky, DM;Zhang, B;Lee, VMY
用于治疗阿尔茨海默病（AD）的策略包括设计用于减少老年斑（SP）形成和/或促进SP清除的疗法。但这些治疗的临床试验受到缺乏有效方法来监测活体AD患者脑中斑块负荷变化的限制。然而.由于SP是淀粉样β肽（A β）的细胞外沉积物，因此可能最终开发出穿过血脑屏障（BBB）并标记SP的放射性配体，从而可以通过当前的成像方法使它们可视化。作为产生这种放射性配体的第一步，我们开发了一种探针，[（反式，反式）-1-溴-2，5-双-（3-羟基羰基-4-羟基）苯乙烯基苯（BSB）]，我们在这里报告，BSB具有以下性质的探针，可以检测SP在体内，首先，BSB灵敏地标记SP在AD脑切片。一下BSB渗透培养物中的活细胞并与细胞内A β聚集体特异性结合。第三，脑内注射后在活体转基因小鼠中建立AD淀粉样变性模型。BSB以高灵敏度和特异性标记由人A β组成的SP。第四，BSB穿过BBB并在静脉注射后标记转基因小鼠整个脑中的许多AD样SP。因此，我们得出结论，BSB是一个适当的起点，为未来的努力，以产生一个生前诊断AD。
Strategies for treating Alzheimer's disease (AD) include therapies designed to decrease senile plaque (SP) formation and/or promote clearance of SPs. but clinical trials of these treatments are limited by the lack of effective methods to monitor changes in plaque burden in the brains of living AD patients. However. because SPs are extracellular deposits of amyloid-beta peptides (A beta), it may be possible to eventually develop radioligands that cross the blood-brain barrier (BBB) and label SPs so they can be visualized by current imaging methods. As a first step toward the generation of such a radioligand, we developed a probe, [(trans,trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene(BSB)], and we report here that BSB has the following properties essential for a probe that can detect SPs in vivo, First, BSB sensitively labels SPs in AD brain sections. Second. BSB permeates living cells in culture and binds specifically to intracellular A beta aggregates. Third, after intracerebral injection in living transgenic mouse models of AD amyloidosis. BSB labels SPs composed of human A beta with high sensitivity and specificity. fourth, BSB crosses the BBB and labels numerous AD-like SPs throughout the brain of the transgenic mice after i.v. injection. Thus, we conclude that BSB is an appropriate starting point for future efforts to generate an antemortem diagnostic for AD.