DNA REPAIR IN AUTOPSY-PROVEN ALZHEIMER'S DISEASE

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Evidence is accumulating of a DNA repair defect in non-neuronal cells of Alz-heimer's patients. The hypothesis has been advanced that this defect might be closely related to the cause of Alzheimer's disease. One of the limitations of many investigations of living cells aimed at discovering the etiology of Alzheimer's disease is the lack of a sufficient number of non-neuronal cell lines available from pathologically-confirmed Alzheimer's disease cases. This study will circumvent this problem by investigating skin fibroblasts collected at autopsy from patients having neuropathological investigations. This study will define the distribution of DNA repair efficiency for 5 different forms of damage produced by 5 different agents (methyl methane sulfonate, x-irradiation, ultraviolet light, mitomycin C and formaldehyde) in 3 age-matched populations, each of about 50 patients, namely autopsy-proven Alzheimer's disease, autopsy-proven non-Alzheimer brain disease (disease controls) and autopsy-proven normal brains (normal controls). The techniques of unscheduled DNA synthesis and alkaline elution sizing of DNA will be used. This study will clearly define the relationship between DNA repair defects and Alzheimer's disease. It will demonstrate whether DNA repair efficiency is a potential cause of the neuronal degeneration, and whether it can be used as a laboratory diagnostic tool for Alzheimer's disease. This study will also provide 30 autopsy-confirmed Alzheimer's disease fibroblast lines to the NIA Cell Repository, Camden, New Jersey, for use by the whole scientific community.