Frontal lobe dysfunction in progressive supranuclear palsy: Evidence for oxidative stress and mitochondrial impairment

Recent data from our laboratory have shown a regionally specific increase i n lipid peroxidation in postmortem progressive supranuclear palsy (PSP) bra in. To extend this finding, we measured activities of mitochondrial enzymes as well as tissue malondialdehyde (MDA) levels in postmortem superior fron tal cortex (Brodmann's area 9; SFC) from 14 pathologically confirmed cases of PSP and 13 age-matched control brains. Significant decreases (-39%) in a lpha-ketoglutarate dehydrogenase complex/glutamate dehydrogenase ratio and significant increases (+36%) in tissue MDA levels were observed in the SFC in PSP; no differences in complex I or complex IV activities were detected. Together, these results suggest that mitochondrial dysfunction and lipid p eroxidation may underlie the frontal metabolic and functional deficits obse rved in PSP.