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Alzheimer's disease cells exhibit defective repair of alkylating agent—induced DNA damage
Author(s) -
Robison Steven H.,
Munzer J. Scott,
Mrcp Rup Tandan,
Bradley Walter G.
Publication year - 1987
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410210306
Subject(s) - dna repair , disease , alzheimer's disease , dna damage , lymphoblast , dementia , dna , senile plaques , degenerative disease , biology , medicine , pathology , cancer research , cell culture , genetics
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 methyl‐methane 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.