Senile dementia of the Alzheimer type is associated with a number of structure and biochemical changes in the central nervous system, including excessive loss of large neurons in certain areas of the brain and deficits in the neurocortical cholinergic and other neurotransmitter systems. The neurotransmitter deficits may be related to the dysfunction and premature death of neurons. One of the possible mechanisms of neuronal dysfunction and death is accumulation of DNA damage. Since a number of DNA repair defects have been detected infibroblasts and lymphocytes of patients with various neuronal degenerative disorders and these defects are thought to be important in the pathogenesis of these disorders, we plan to examine fibroblast strains of Alzheimer's disease patients for evidence of excessive DNA damage and for defects in DNA repair. The incidence of DNA lesions and their type will be determined in Alzheimer's strains and in age- and sex-matched control strains, using alkaline elution and neutral elution methods. DNA damage will be induced with MNNG and the repair monitored by the above filter elution methods. The findings of excessive accumulation of DNA damage, due either to irreparable types of damage or to defects in DNA repair, would provide a rationale for examining cells of patients with senile dementia of Alzheimer type, using a battery of DNA-damaging agents. Such studies may result in identifying sub-classes of SDAT, establishing hereditary patterns, clarifying pathogenesis and may provide a rationale for new types of therapeutic interventions.