Feb 18, 2010

Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons

Neuro-degenerative Diseases
Xinglong WangXiongwei Zhu

Abstract

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.

  • References9
  • Citations42

References

Mentioned in this Paper

Pathogenic Aspects
Axonal Transport
Transfection
Abnormal Degeneration
Pathogenesis
APP protein, human
CaM-BP(80)
Neurons
Nerve Degeneration
APP wt Allele

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