PRECURSOR OF AMYLOID PROTEIN IN ALZHEIMER-DISEASE UNDERGOES FAST ANTEROGRADE AXONAL-TRANSPORT
PRECURSOR OF AMYLOID PROTEIN IN ALZHEIMER-DISEASE UNDERGOES FAST ANTEROGRADE AXONAL-TRANSPORT
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DOI：
10.1073/pnas.87.4.1561
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发表时间：
1990-02-01
影响因子：
11.1
通讯作者：
PRICE, DL
中科院分区：
文献类型：
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作者：
KOO, EH;SISODIA, SS;PRICE, DL
在老年人和阿尔茨海默病患者的大脑中，老年斑中淀粉样蛋白的沉积物位于神经突起附近。这种细胞外淀粉样蛋白的主要成分是β/ A4是一种来源于较大淀粉样前体蛋白（APP）的肽，在脑和全身器官中活跃表达。导致APP蛋白水解形成β/β-淀粉样蛋白的机制A4，以前称为β-淀粉样蛋白和随后的肽在脑中的沉积是未知的。 如果β/老年斑中的A4来源于神经元合成的APP，并沉积在远离合成位点的位置，那么APP必须从神经元细胞体转运到接近淀粉样蛋白沉积物的远端神经突起。在这项研究中，使用几种免疫检测方法，我们证明，APP是在大鼠周围神经系统的神经元轴突运输。此外，我们的研究表明，APP是通过快速顺行组件。 这些发现与β/γ-淀粉样蛋白的神经元起源的假设一致。A4，其中淀粉样蛋白沉积在老年个体和阿尔茨海默病病例的脑实质中。在这种情况下，我们认为APP是在神经元中合成的，并传递到营养不良的神经末梢，随后改变APP的局部加工导致脑淀粉样蛋白的沉积。
In the brains of aged humans and cases of Alzheimer disease, deposits of amyloid in senile plaques are located in proximity to nerve processes. The principal component of this extracellular amyloid is .beta./A4, a peptide derived from a larger amyloid precursor protein (APP), which is actively expressed in brain and systemic organs. Mechanisms that result in the proteolysis of APP to form .beta./A4, previously termed .beta.-amyloid protein, and the subsequent deposition of the peptide in brain are unknown. If .beta./A4 in senile plaques is derived from neuronally synthesized APP and deposited at locations remote from sites of synthesis, then APP must be transported from neuronal cell bodies to distal nerve processes in proximity to deposits of amyloid. In this study, using several immunodetection methods, we demonstrate that APP is transported axonally in neurons of the rat peripheral nervous system. Moreover, our investigations show that APP is transported by means of the fast anterograde component. These findings are consistent with the hypothesis of a neuronal origin of .beta./A4, in which amyloid is deposited in the brain parenchyma of aged individuals and cases of Alzheimer disease. In this setting, we suggest that APP is synthesized in neurons and delivered to dystrophic nerve endings, where subsequent alterations of local processing of APP result in deposits of brain amyloid.