title: Preclinical Alzheimer disease: brain oxidative stress, Abeta peptide and proteomics.
abstract: Alzheimer disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory loss and subsequent dementia and neuropathologically by senile plaques, neurofibrillary tangles, and synapse loss. Interestingly, a small percentage of individuals with normal antemortem psychometric scores meet the neuropathological criteria for AD (termed 'preclinical' AD (PCAD)). In this study, inferior parietal lobule (IPL) from PCAD and control subjects was compared for oxidative stress markers by immunochemistry, amyloid beta peptide by ELISA, and identification of protein expression differences by proteomics. We observed a significant increase in highly insoluble monomeric Abeta42, but no significant differences in oligomeric Abeta nor in oxidative stress measurements between controls and PCAD subjects. Expression proteomics identified proteins whose trends in PCAD are indicative of cellular protection, possibly correlating with previous studies showing no cell loss in PCAD. Our analyses may reveal processes involved in a period of protection from neurodegeneration that mimic the clinical phenotype of PCAD.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Aluise
authors.forename: Renã A Sowell
authors.initials: RA
authors.lastname: Robinson
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000378:metabolism*; D050050:Protein Carbonylation; D040901:Proteomics / Q000379:methods*; D013057:Spectrum Analysis / Q000379:methods; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C002744:3-nitrotyrosine; D014443:Tyrosine
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