Snow A D, Sekiguchi R, Nochlin D, Fraser P, Kimata K, Mizutani A, Arai M, Schreier W A, Morgan D G
Department of Pathology, University of Washington, Seattle 98195.
Neuron. 1994 Jan;12(1):219-34. doi: 10.1016/0896-6273(94)90165-1.
A consistent rat model for the study of the consequences of congophilic and fibrillar A beta-amyloid in brain has been developed. One hundred percent of animals receiving infusions of synthetic beta-amyloid protein (A beta 1-40) plus a specific heparan sulfate proteoglycan (HSPG) for 1 week or 7 weeks (following 2 week infusions) demonstrated Congo red and thioflavin S-positive deposits adjacent to the infusion site. Extracellular amyloid fibrils were identified by electron microscopy and were immunogold decorated with A beta antibody. Significant increases in Congo red staining were observed in animals infused with A beta plus HSPG versus those infused with only A beta. Infusion of A beta alone was variable with respect to congophilic amyloid persistence, which occurred in 50% of animals and only when endogenous HSPGs accumulated at A beta deposition sites. By 7 weeks, only animals infused with A beta plus HSPG demonstrated compaction of the Congo red material from amorphous, wispy deposits (at 1 week) to stellate deposits resembling a Maltese cross. These spherical amyloid deposits were very similar to Congo red-stained amyloid plaques in human Alzheimer's disease brain, and in vitro data suggest that they were probably formed in vivo following interactions with endogenous brain components.
已建立一种用于研究脑内嗜刚果红性和纤维状β-淀粉样蛋白后果的一致大鼠模型。接受合成β-淀粉样蛋白（Aβ1-40）加特定硫酸乙酰肝素蛋白聚糖（HSPG）输注1周或7周（在2周输注后）的动物，100%在输注部位附近出现刚果红和硫黄素S阳性沉积物。通过电子显微镜鉴定出细胞外淀粉样纤维，并用Aβ抗体进行免疫金标记。与仅输注Aβ的动物相比，输注Aβ加HSPG的动物刚果红染色显著增加。单独输注Aβ时，嗜刚果红性淀粉样蛋白的持续性存在差异，仅在50%的动物中出现，且仅当内源性HSPG在Aβ沉积部位积累时才会出现。到7周时，只有输注Aβ加HSPG的动物显示刚果红物质从无定形、纤细沉积物（1周时）压实为类似马耳他十字的星状沉积物。这些球形淀粉样沉积物与人类阿尔茨海默病脑中刚果红染色的淀粉样斑块非常相似，体外数据表明它们可能是在与脑内源性成分相互作用后在体内形成的。
