Abstract: The pathological features of Alzheimer`s disease include deposition of senile plaques in different brain zones formed by aggregates of fibrillar Aß peptide (AßP), a neurotoxic metabolic product. In this study we used the soluble form of fragment 25-35 of AßP, that includes methionine 35, side chain of AßP, to investigate the role of redox state of Met-35 on the pathogenesis of AD, because this residue in AßP is the most susceptible to oxidation in vivo. The data obtained evidenced that Aß(25-35) peptide determines a loss of PC12 cells viability determining mitochondrial damage with a possible trigger of pro-apoptotic signals. In particular, the following parameters were examined: cytochrome c release, mitochondrial membrane potential (ΔΨm) and mitochondrial respiration. In this study, three different peptides have been used: Aß(25-35) with methionine 35 in the reduced state, oxidized to sulfoxide and/or substituted with norleucine. We conclude that alteration in the mitochondrial functionality might be a contributing factor to the pathogenesis of AD and the amplitude of the effects elicited by Aß peptide is modulated by the redox state of methionine.