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Updated: Jun 16, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons
Xinglong Wang1, George Perry, Mark A Smith
1Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
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.
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