APP and PS-1 mutations induce brain oxidative stress independent of dietary cholesterol: implications for Alzheimer's disease.
Epidemiological and biochemical studies strongly implicate a role for cholesterol in the pathogenesis of Alzheimer's disease (AD). Mutation in the PS-1 and APP genes, which increases production of the highly amyloidogenic amyloid beta-peptide (Abeta42), is the major cause of familial AD. The AD brain is under significant oxidative stress, including protein oxidation and lipid peroxidation. In the present study, protein oxidation and lipid peroxidation were compared in the brain homogenates from knock-in mice expressing mutant human PS-1 and APP in relation to the intake of dietary cholesterol. The APP and PS-1 mice displayed increased oxidative stress as measured by protein oxidation and lipid peroxidation, independent of dietary cholesterol. These results are discussed with reference to proposed therapeutic strategies of AD.
Mohmmad Abdul
Hafiz
H
Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
Wenk
Gary L
GL
Gramling
McGann
M
Hauss-Wegrzyniak
Beatrice
B
Butterfield
D Allan
DA
D000447:Aldehydes / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D015151:Immunoblotting / Q000379:methods; D015227:Lipid Peroxidation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D053764:Presenilin-1
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D002791:Cholesterol, Dietary; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C027576:4-hydroxy-2-nonenal