Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Neurodegener Dis. 2010;7(1-3):56-9. doi: 10.1159/000283484. Epub 2010 Feb 13.
Alzheimer's disease (AD) is the most prevalent form of dementia predominantly affecting the elderly. It is believed that soluble amyloid-beta (Abeta) oligomers are involved in the pathogenesis of AD, yet the underlying mechanisms remain elusive.
Emerging evidence suggests that mitochondrial dysfunction likely plays a critical role in Abeta-induced neuronal degeneration. Previously, we demonstrated that Abeta-derived diffusible ligands (ADDLs) induce reduced mitochondrial density in neurites, and we suspect that an impaired mitochondrial trafficking might be involved, which is tested in this study.
Using live cell imaging, anterograde and retrograde transport of mitochondria in primary hippocampal neurons treated with sub-lethal doses of ADDLs was measured.
We found that ADDLs induced significant impairment in both anterograde and retrograde transport of mitochondria along axons.
These results suggest that an impaired mitochondrial transport likely contributes to ADDL-induced abnormal mitochondrial distribution and dysfunction and also reinforce the idea that axonal transport is likely involved in AD pathogenesis.
阿尔茨海默病（AD）是最常见的痴呆症形式，主要影响老年人。据信可溶性淀粉样蛋白-β（Abeta）寡聚物参与 AD 的发病机制，但潜在机制仍不清楚。
新出现的证据表明，线粒体功能障碍可能在 Abeta 诱导的神经元变性中起关键作用。之前，我们证明 Abeta 衍生的可扩散配体（ADDLs）在神经突中诱导线粒体密度降低，我们怀疑可能涉及受损的线粒体运输，本研究对此进行了测试。
使用活细胞成像技术，测量用亚致死剂量的 ADDLs 处理的原代海马神经元中线粒体的顺行和逆行运输。
我们发现 ADDLs 诱导了沿着轴突的线粒体顺行和逆行运输的显著损伤。
这些结果表明，受损的线粒体运输可能导致 ADDL 诱导的异常线粒体分布和功能障碍，并进一步强化了轴突运输可能参与 AD 发病机制的观点。
