Recently, it has been shown that mitochondrial dysfunction and oxidative stress play important roles in the pathogenesis of neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes – the end products of lipid peroxidation, is considered to exert protective function in mitochondria. The aim of our study was to use the methods of differential proteomics in concert with molecular and morphological techniques to elucidate the changes in the frontal cortex and hippocampus of apolipoprotein E knockout (apoE-/-) mice (an animal model of the early stages of Alzheimer’s disease) upon treatment with Alda-1 – a small molecular weight activator of ALDH2.