Elevated levels of 3-nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: implications for the role of nitration in the progression of Alzheimer's disease.
A number of studies reported that oxidative and nitrosative damage may be important in the pathogenesis of Alzheimer's disease (AD). However, whether oxidative damage precedes, contributes directly, or is secondary to AD pathogenesis is not known. Amnestic mild cognitive impairment (MCI) is a clinical condition that is a transition between normal aging and dementia and AD, characterized by a memory deficit without loss of general cognitive and functional abilities. Analysis of nitrosative stress in MCI could be important to determine whether nitrosative damage directly contributes to AD. In the present study, we measured the level of total protein nitration to determine if excess protein nitration occurs in brain samples from subjects with MCI compared to that in healthy controls. We demonstrated using slot blot that protein nitration is higher in the inferior parietal lobule (IPL) and hippocampus in MCI compared to those regions from control subjects. Immunohistochemistry analysis of hippocampus confirmed this result. These findings suggest that nitrosative damage occurs early in the course of MCI, and that protein nitration may be important for conversion of MCI to AD.
Butterfield
D Allan
DA
Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA. dabcns@uky.edu <dabcns@uky.edu>
Reed
Tanea T
TT
Perluigi
Marzia
M
De Marco
Carlo
C
Coccia
Raffaella
R
Keller
Jeffrey N
JN
Markesbery
William R
WR
Sultana
Rukhsana
R
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000647:Amnesia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010296:Parietal Lobe / Q000378:metabolism / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D009566:Nitrates; C002744:3-nitrotyrosine; D014443:Tyrosine