Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation
Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation
复制标题
DOI：
10.1073/pnas.0903200106
复制
发表时间：
2009-08-04
影响因子：
11.1
通讯作者：
Jucker, Mathias
中科院分区：
文献类型：
--
作者：
Eisele, Yvonne S.;Bolmont, Tristan;Jucker, Mathias
尽管A β的异常聚合在阿尔茨海默病的早期致病级联中的重要性，但对体内A β聚集的诱导知之甚少。在这里，我们表明，通过注射稀释的A β脑提取物，可以在APP 23转基因小鼠的许多不同脑区诱导脑β淀粉样变性。一旦外源性诱导淀粉样蛋白生成过程，诱导的A β沉积的性质由宿主的脑区域决定。由于这些观察结果使人联想到朊病毒样机制，我们随后研究了外周和全身接种或脑内植入预先涂有微量含A β脑提取物的不锈钢丝是否也可诱导脑β淀粉样变性。结果显示，口服、静脉内、眼内和鼻内接种在APP 23转基因小鼠中未产生可检测的脑β-淀粉样变性诱导。相反，大脑β-淀粉样变性通过A β污染的钢丝传播。值得注意的是，等离子体灭菌，而不是在植入前煮沸导丝，防止了β-淀粉样变性的诱导。我们的研究结果表明，微量的A β直接接触中枢神经系统的脑材料可以诱导脑β-淀粉样变性，但系统的细胞机制朊病毒的摄取和运输到中枢神经系统可能不适用于A β。
Despite the importance of the aberrant polymerization of A beta in the early pathogenic cascade of Alzheimer's disease, little is known about the induction of A beta aggregation in vivo. Here we show that induction of cerebral beta-amyloidosis can be achieved in many different brain areas of APP23 transgenic mice through the injection of dilute A beta-containing brain extracts. Once the amyloidogenic process has been exogenously induced, the nature of the induced A beta-deposition is determined by the brain region of the host. Because these observations are reminiscent of a prion-like mechanism, we then investigated whether cerebral beta-amyloidosis also can be induced by peripheral and systemic inoculations or by the intracerebral implantation of stainless steel wires previously coated with minute amounts of A beta-containing brain extract. Results reveal that oral, intravenous, intraocular, and intranasal inoculations yielded no detectable induction of cerebral beta-amyloidosis in APP23 transgenic mice. In contrast, transmission of cerebral beta-amyloidosis through the A beta-contaminated steel wires was demonstrated. Notably, plasma sterilization, but not boiling of the wires before implantation, prevented the induction of beta-amyloidosis. Our results suggest that minute amounts of A beta-containing brain material in direct contact with the CNS can induce cerebral beta-amyloidosis, but that systemic cellular mechanisms of prion uptake and transport to the CNS may not apply to A beta.