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Amyloid beta induces mitochondrial dysfunction in a dose-dependent manner
Alzheimer’s disease is associated with defects in mitochondrial function. We have previously reported that PC12 cells bearing the Swedish Alzheimer APP mutation (APPsw) show a significantly decreased mitochondrial membrane potential after exposure to oxidative and nitrosative stress compared to human wild-type APP-bearing cells (APPwt) and empty vector-transfected cells (vct) (1).
Here, we investigated the effects of mitochondrial respiratory chain inhibitors on changes in mitochondrial membrane potential. Interestingly, we could show that the respiratory chain complexes II-V in APPsw cells are more vulnerable against mitochondrial membrane potential changes than vct cells. Moreover, complex IV and V of APPwt cells are more sensitive than vct cells but as sensitive as APPsw cells. Additionally, our data demonstrate reduced basal ATP levels in the following order: APPsw < APPwt < vct. These data suggest that increasing amyloid ß production from APPwt cells to APPsw cells results in a dose-dependent decline in ATP levels.
supported by grants of Alzheimer Forschung Initiative (AFI), Dr. Robert Pfleger, Landesgraduiertenförderung Hessen
(1) Marques CA, Keil U et al. J Biol Chem. 2003 May 1 [Epub ahead of print]