Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease

Although amyloid-beta peptide (Abeta) is the neurotoxic species implicated in the pathogenesis of Alzheimer's disease (AD), mechanisms through which intracellular Abeta impairs cellular properties, resulting in neuronal dysfunction, remain to be clarified. Here we demonstrate that intracellular Abeta is present in mitochondria from brains of transgenic mice with targeted neuronal overexpression of mutant human amyloid precursor protein and AD patients. Abeta progressively accumulates in mitochondria and is associated with diminished enzymatic activity of respiratory chain complexes (III and IV) and a reduction in the rate of oxygen consumption. Importantly, mitochondria-associated Abeta, principally Abeta42,…

• MJ
  Michael J. Fox Foundation for Parkinson's Research

  Awards: NS 042855, P50 AG08702, AG16736, P01 AG17490
• SO
  Sundhed og Sygdom, Det Frie Forskningsråd
• H
  Hørslev-Fonden