Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde

Oxidative stress is thought to play a major role in the pathogenesis of Alz heimer's disease (AD). Although there is strong post-mortem and experimenta l evidence of oxidative damage occurring in AD brains, the use of markers i n the peripheral circulation to show oxidative stress is less convincing. W e examined plasma from AD patients for markers of increased oxidative stres s. We report elevated levels of 4-hydroxy-nonenal (4-HNE) in AD patients co mpared to controls (median 20.6, IQR 6.0-25.2 vs. 7.8, 3.3-14.5 mu mol/l, r espectively; p = 0.001) but not malondialdehyde (MDA), and lower levels of ascorbate in AD plasma when compared to age-matched controls (9.9, 6.0-33.7 vs. 24.2, 13.9-48.6 mu mol/l; p < 0.05). Levels of 4-HNE in AD patients we re inversely related to ascorbate (r = -0.337; p = 0.07) and Folstein Mini- Mental State Examination (MMSE) (r = -0.474; P=0.015). The concentration of protein sulphydryls, free-radical scavengers, was directly related to the MMSE result (r = 0.427; p = 0.03). Increased production of 4-HNE indicates increased oxidative stress (lipid peroxidation), which is not evident using the more common marker MDA. This elevation of 4-HNE was related to the deg ree of cognitive impairment (MMSE).