Lipoperoxidation is selectively involved in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder charac terized by extensive neurofibrillary tangle (NFT) formation and neuronal lo ss in selective neuronal populations. Currently, no clues to the biological events underlying the pathological process have emerged. In Alzheimer dise ase (AD), which shares with PSP the occurrence of NFTs, advanced glycation end products (AGEs) as well as oxidation adducts have been found to be incr eased in association with neurofibrillary pathology. The presence and the a mount of lipid and protein oxidation markers, as well as of pyrraline and p entosidine, 2 major AGEs, was assessed by biochemical, immunochemical, and immunocytochemical analysis in midbrain tissue from 5 PSP cases, 6 sporadic AD cases, and 6 age-matched control cases. The levels of 4-hydroxynonenal (HNE) and thiobarbituric acid reactive substances (TBARS), 2 major products of lipid peroxidation, were significantly increased by 1.6-fold (p < 0.04) and 3.9-fold (p < 0.01), respectively, in PSP compared with control tissue s, whereas in AD only TEARS were significantly increased. In PSP tissue the intensity of neuronal HNE immunoreactivity was proportional to the extent of abnormal aggregated tau protein. The amount of protein oxidation product s and AGEs was instead similar in PSP and control tissues. In AD, a higher but not significant level of pyrraline and pentosidine was measured, wherea s the level of carbonyl groups was doubled. These findings indicate that in PSP, unlike in AD, lipid peroxidation is selectively associated with NFT f ormation. The intraneuronal accumulation of toxic aldehydes may contribute to hamper tau degradation, leading to its aggregation in the PSP specific a bnormal filaments.