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


OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Xinglong
X
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Perry
George
G
Smith
Mark A
MA
Zhu
Xiongwei
X
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D014162:Transfection / Q000379:methods; D000099291:Adducins
D016229:Amyloid beta-Peptides; D002148:Calmodulin-Binding Proteins; D008164:Luminescent Proteins; C102021:ADD3 protein, human; D000099291:Adducins; C413663:fluorescent protein 583