Increased susceptibility to plasma lipid peroxidation in Alzheimer disease patients.
Oxidative stress, linked to Abeta-lipid interactions, plays a pathogenetic role in Alzheimer's disease. We investigated modifications of lipid peroxidation products in plasma of 52 AD patients, 42 healthy controls and 16 patients with amyotrophic lateral sclerosis, a neurodegenerative disease where oxidative stress also plays a pathogenetic role. Final lipid peroxidation products were measured in plasma by thiobarbituric acid reactive substances (TBARS) assay before and after ex vivo oxidative stress catalysed by copper. There were no significant changes at basal conditions, but after copper-induced oxidation TBARS levels were higher in AD patients (19.0 microM +/- 2.2) versus both controls (5.2 microM +/- 0.8, p<0.001) and ALS patients (7.6 microM +/- 2.1, p<0.01). Stimulated TBARS levels were significantly higher in mild and moderate AD (p<0.0001) with respect to controls, but not in severe AD patients, with a significant inverse correlation between disease severity and lipid peroxidation (p<0.005, r2=0.21). Treatment of a subgroup (13) of mild and moderate AD patients with vitamin C and E for three months decreased plasma lipoperoxidation susceptibility by 60%. Thus, oxidative stress, expressed as ex vivo susceptibility to lipid peroxidation, appears to be an early phenomenon, probably related to AD pathogenetic mechanisms.
Galbusera
Carmen
C
Department of Neuroscience and Biomedical Technologies, University of Milano, Bicocca, Milan, Italy.
Facheris
Maurizio
M
Magni
Fulvio
F
Galimberti
Gloria
G
Sala
Gessica
G
Tremolada
Lucia
L
Isella
Valeria
V
Guerini
Franca Rosa
FR
Appollonio
Ildebrando
I
Galli-Kienle
Marzia
M
Ferrarese
Carlo
C
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood; D000975:Antioxidants / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics; D001205:Ascorbic Acid / Q000627:therapeutic use; D016022:Case-Control Studies; D003300:Copper / Q000494:pharmacology; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D001057:Apolipoproteins E; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D003300:Copper; D001205:Ascorbic Acid