Molecular mechanisms of the membrane disorder in the senile dementia due to free radical

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Senile dementia of cerebrovascular type is caused by ischemic injury of brain due to free radical-related lipid peroxide. First of all we investigated the methods for identification and quantification of cholesterol hydroperoxide. Next, we collected brain tissue of dementia and healthy subjects at autopsy. Then we divided into six regions, frontal cortex and white matter, parietotemporal cortex and white matter, and occipital cortex and white matter. Each tissue was homogenized and lipid was extracted. We identified 7-hydroperoxycholestero l 7-hydroxycholesterol, 7-ketocholesterol, and 5,6-epoxycholesterol by high performance liquid chromatography-mass spectrometory. In addtion we quantified 7 alpha -and 7- beta hydroperoxycholesterol by high performance liquid chromatography with chemiluminescent detection. We found an accumulation of 7-hydroperoxycholesterol in the brain of senile dementia. The accumulation was evident in parietotemporal white matter among the brain regions.