| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Research Abstract |
Increasing evidence implicates oxidative stress in the aging process of the brain as well as in Alzheimer's disease (AD) and Down's syndrome (DS). We used an in situ approach to identify the oxidized nucleoside, 8-hydroxyguanosine (8OHG; the 1F7 antibody) in the cerebral cortex of familial AD with presenflin-1 mutations (n=12, age 47-81 y), sporadic AD (n = 22, 57-93 y), DS (n=22, 0.3-64 y), and non-demented patients (n=40, 0.3-86 y). Relative intensity measurements of 80HG immunoreactivity (Q500IW-EX, Leica) showed there was an age-related increase of neuronal 8OHG in non-demented patients. In sporadic AD and DS, but not in familial AD, neuronal 8OHG significantly increased compared to age-matched controls. Interestingly, significant 8OHG elevation temporally precedes the significant increase of amyloid β deposition in DS, and the levels of 8OHG inversely correlated with % amyloid β burden in sporadic AD and DS. Neuronal nucleic acid oxidation is an age-related event as well as an upstream event in the pathological cascade of sporadic AD and DS. Deposition of Aβmay be related to a compensatory response to sustained oxidative stress in AD and DS.
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