title: Oxidative modification of proteins in the frontal cortex of Alzheimer's disease brain.
abstract: There is a large body of evidence highlighting the importance of oxidative stress in the pathogenesis of Alzheimer's disease (AD). We have previously standardised a method that can be applied to study oxidative changes in individual brain proteins by using two-dimensional oxyblots (Korolainen MA, Goldsteins G, Alafuzoff I, Koistinaho J, Pirttilä T. Proteomic analysis of protein oxidation in Alzheimer's disease brain. Electrophoresis 2002;23(19):3428-33). Here we have identified proteins that exhibited oxidative changes in AD when compared to age-matched controls and these protein changes have been further examined in relation to the neuropathological data. Indeed, several Tris-HCl soluble proteins tended to be less oxidised in AD when compared to controls. Two enzymes, mitochondrial glutamate dehydrogenase and cytosolic malate dehydrogenase, were increased in amount but showed significantly decreased degree of oxidation in AD brains when compared to controls. Furthermore, some changes related to the amounts or oxidation statuses of proteins were associated with the duration of the clinical impairment and also with the neuropathology. These results do not contradict the hypothesis of increased oxidative stress in AD but may represent co-existing compensatory changes in response to oxidative stress.
authors.affiliation: Department of Neuroscience and Neurology, University of Kuopio, and Department of Neurology, Kuopio University Hospital, Kuopio, Finland. minna.korolainen@uku.fi
authors.forename: Minna A
authors.initials: MA
authors.lastname: Korolainen
authors.forename: Gundars
authors.initials: G
authors.lastname: Goldsteins
authors.forename: Tuula A
authors.initials: TA
authors.lastname: Nyman
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Jari
authors.initials: J
authors.lastname: Koistinaho
authors.forename: Tuula
authors.initials: T
authors.lastname: Pirttilä
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D002102:Cadaver; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species