Alzheimer's disease cells exhibit defective repair of alkylating agent-induced DNA damage

Abstract

The most common cause of senile and presenile dementia is Alzheimer's disease, a disorder with an undetermined cause. A number of studies have indicated that neurons from patients with Alzheimer's disease have decreased ribonucleic acid levels and reduced protein synthesis. Recent studies using lymphoblasts from patients with Alzheimer's disease have indicated that these cells are more sensitive to deoxyribonucleic acid (DNA)-alkylating agents. We have used cell survival, unscheduled DNA synthesis, and alkaline elution to assess the capacity for DNA repair in skin fibroblasts from normal control subjects, control subjects with central nervous system disease, and patients with Alzheimer's disease. Our results indicate that the Alzheimer's disease cells, unlike normal cells, fail to repair methylmethane sulfonate-induced DNA damage. Both normal and Alzheimer's disease cells are able to ameliorate the effects of ultraviolet light. These results indicate that a specific pathway for DNA repair is affected in Alzheimer's disease. The repair defect may be related to the cause of the disease or may be the cause of the disease.