Mitochondrial dysfunction induced by disease relevant AβPP and tau protein mutations

Abstract

Alzheimer's disease is characterized by two major pathological hallmarks: extracellular plaques consisting of amyloid beta peptide and neurofibrillary tangles composed of hyperphosphorylated tau protein. Mutations in the amyloid beta-protein precursor (AbetaPP) have been linked to familial Alzheimer's disease. They are leading to increased amyloid beta production. Mutations in the tau gene have not been described in AD, but are leading to formation of neurofibrillary tangles very similar to filaments in AD brains, and are therefore of increasing relevance in AD research. Interestingly, our data indicate that mutations in AbetaPP gene and mutations in tau gene induce mitochondrial dysfunction and oxidative stress in cell culture models and transgenic mice. Thus, both Alzheimer relevant protein alterations seem to have synergistic actions probably at the level of mitochondria leading to synaptic dysfunction and apoptotic cell death.