The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease

Alzheimer's disease (AD) has been hypothesized to be associated with oxidat ive stress. in this study, the expression of key oxidative stress-handling genes was studied in hippocampus, inferior parietal lobule, and cerebellum of 10 AD subjects and 10 control subjects using reverse transcriptase-polym erase chain reaction (RT-PCR). The content of Mn-, Cu,Zn-superoxide dismuta ses (Mn- and Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-rx), a nd glutathione reductase (GSSG-R) mRNAs, and the "marker genes" (beta-actin and cyclophilin) mRNAs was determined. This study suggests that gene respo nses to oxidative stress can be significantly modulated by the general decr ease of transcription in the AD brain. To determine if the particular oxida tive stress handling gene transcription was induced or suppressed in AD, th e "oxidative stress-handling gene/beta-actin" ratios were quantified and co mpared with control values in all brain regions studied. The Mn-SOD mRNA/be ta-actin mRNA ratio was unchanged in all regions of the AD brain studied, b ut an increase of the Cu,Zn-SOD mRNA/beta-actin mRNA ratio was observed in the AD inferior parietal lobule. The levels of peroxidation handling (CAT, GSH-Px, and GSSG-R) mRNAs normalized to beta-actin mRNA level were elevated in hippocampus and inferior parietal lobule, but not in cerebellum of AD p atients, which may reflect the protective gene response to the increased pe roxidation in the brain regions showing severe AD pathology. The results of this study suggest that region-specific differences of the magnitude of RO S-mediated injury rather than primary deficits of oxidative stress handling gene transcription are likely to contribute to the variable intensity of n eurodegeneration in different areas of AD brain.