Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease

Objective: To investigate the levels of glutathione transferase (GST), a pr otective enzyme against aldehydes, and especially 4-hydroxynonenal (HNE) in the brain and ventricular CSF of autopsied AD and normal control subjects. Background: Studies have implicated increased levels of oxidative stress i n the brain in the pathogenesis of AD. Decreased levels of polyunsaturated fatty acids and increased levels of markers of lipid peroxidation have been reported in the brain in AD, particularly in areas severely affected in th e disease. HNE, one marker of lipid peroxidation, is neurotoxic in neuronal culture and in vivo and is elevated in AD brain and CSF. Methods: We measu red levels of GST activity and protein in multiple brain regions and ventri cular CSF in short-postmortem-interval AD patients and age-matched prospect ively evaluated control subjects. Results: A decrease in GST activity in al l brain areas was observed in AD compared with controls with significant de creases in the amygdala, hippocampus and parahippocampal gyrus, inferior pa rietal lobule, and nucleus basalis of Meynert. Levels of GST protein also w ere depleted in most brain regions in AD. A significant decrease in GST act ivity and protein levels was also found in ventricular CSF in AD. Conclusio n: Reduced levels of GST, a protective mechanism against HNE, may have a ro le in the pathogenesis of neuron degeneration in AD.