title: Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons.
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.
  
  
  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.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Wang
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D002148:Calmodulin-Binding Proteins; D008164:Luminescent Proteins; C102021:ADD3 protein, human; D000099291:Adducins; C413663:fluorescent protein 583