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Neurodegener Dis. 2010;7(1-3):56-9. doi: 10.1159/000283484. Epub 2010 Feb 13.

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

Author information

1
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.

Abstract

BACKGROUND:

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.

OBJECTIVES:

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.

METHODS:

Using live cell imaging, anterograde and retrograde transport of mitochondria in primary hippocampal neurons treated with sub-lethal doses of ADDLs was measured.

RESULTS:

We found that ADDLs induced significant impairment in both anterograde and retrograde transport of mitochondria along axons.

CONCLUSION:

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.

PMID:
20160460
PMCID:
PMC2859232
DOI:
10.1159/000283484
[Indexed for MEDLINE]
Free PMC Article

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