Characterization of neuronal dystrophy induced by fibrillar amyloid β:: Implications for Alzheimer's disease
Characterization of neuronal dystrophy induced by fibrillar amyloid β:: Implications for Alzheimer's disease
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DOI：
10.1016/s0306-4522(02)00241-5
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Busciglio, J
中科院分区：
文献类型：
--
作者：
Grace, EA;Rabiner, CA;Busciglio, J
淀粉样蛋白沉积、神经元营养不良和突触丢失是阿尔茨海默病（AD）的特征性病理特征。我们使用皮层神经元培养来评估纤维状淀粉样蛋白β（Abeta）的营养不良作用及其与神经毒性和突触丢失的关系。用纤维状Abeta处理导致培养物中存在的大多数神经元发生神经炎性营养不良。形态分析和活力测定表明，神经元营养不良出现显着更早，在较低的Abeta浓度比神经毒性，这表明这两种效果是由不同的细胞机制独立产生。营养不良特征的发展需要Abeta原纤维形成，并且不依赖于Abeta序列中RHDS粘附结构域的存在。最后，突触素免疫反应性密度的急剧下降与存活神经元的营养不良变化密切相关。这些结果表明，纤维状A β诱导的异常可塑性变化和突触完整性丧失可能在AD病理的发展中发挥重要作用。(C)2002年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Amyloid deposition, neuronal dystrophy and synaptic loss are characteristic pathological features of Alzheimer's disease (AD). We have used cortical neuronal cultures to assess the dystrophic effect of fibrillar amyloid beta (Abeta) and its relationship kith neurotoxicity and synaptic loss. Treatment with fibrillar Abeta led to the development of neuritic dystrophy in the majority of the neurons present in the culture. Morphometric analysis and viability assays showed that neuronal dystrophy appeared significantly earlier and at lower Abeta concentrations than neurotoxicity, suggesting that both effects are generated independently by different cellular mechanisms. The development of dystrophic features required Abeta fibril formation and did not depend on the presence of the RHDS adhesive domain in the sequence of Abeta. Finally, a dramatic reduction in the density of synaptophysin immunoreactivity was closely associated with dystrophic changes in viable neurons.These results suggest that aberrant plastic changes and loss of synaptic integrity induced by fibrillar Abeta may play a significant role in the development of AD pathology. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.