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Multiple studies demonstrate increased lipid peroxidation ( Markesbery et al., 1998 Lovell et al., 2001 McGarth, 2001 Reich, 2001 Markesbery et al., 2005 Williams et al., 2006), protein oxidation (reviewed in ( Sultana et al., 2006 Sultana et al., 2009) and DNA (reviewed in ( Lovell et al., 2007) and RNA oxidation ( Nunomura et al., 2001 Shan et al., 2003 Ding et al., 2006 Shan et al., 2006) in vulnerable regions of brain in late-stage AD (LAD).
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Increasing evidence supports a role for oxidative damage in the pathogenesis of Alzheimer’s disease (AD). Overall, the data suggest oxidative damage to nucleic acids and a compensatory increase in OGG1 expression occur early in the pathogenesis of AD. Quantification of OGG1 showed significantly elevated mRNA in PCAD SMTG and a trend toward elevated immunostaining in PCAD HPG. Results show significantly increased (p < 0.05) 8-OHG immunostaining in DNA and RNA of PCAD HPG and significantly increased 8-OHG in PCAD SMTG. To determine if increased DNA oxidation is associated with altered repair capacity, levels of OGG1 protein in HPG were measured by immunohistochemistry and levels of OGG1 mRNA were measured in SMTG using quantitative PCR. To determine if DNA or RNA oxidation are significantly elevated in PCAD brain we quantified 8-OHG in sections of hippocampus/parahippocamapal gyri in PCAD and NC subjects using immunohistochemistry and confocal microscopy and in superior and middle temporal gyri (SMTG) using gas chromatography/mass spectrometry. Recently, a preclinical stage of AD (PCAD) has been described in which subjects show no overt clinical manifestations of AD but demonstrate significant AD pathology at autopsy. Previous studies show increased oxidative DNA and RNA damage and diminished 8-oxoguanine glycosylase (OGG1) mediated base excision repair in vulnerable brain regions of mild cognitive impairment and late-stage Alzheimer’s disease (LAD) subjects compared to normal control (NC) subjects.