Superoxide dismutase activity in Alzheimer's disease: possible mechanism for paired helical filament formation.

Activity of the free radical scavenging enzyme, superoxide dismutase (SOD-1), was determined in fibroblast cell lines derived from familial Alzheimer's patients, trisomy 21 patients and normal controls. In the present study, SOD-1 activity was significantly elevated by 30% in Alzheimer's cell lines when compared to normal euploid cell lines. As SOD-1 activity is known to be elevated about 50% in trisomy 21 patients, these cell lines were included as a control for tissue culture and assay conditions. In the present study, SOD-1 activity was significantly increased by 42 +/- 11% in trisomy 21 patients. The elevation in SOD-1 activity observed in the familial Alzheimer's patients supports the theory that paired helical filaments are synthesized in Alzheimer's disease by free radical hydroxylation of proline residues in paired helical filament precursor protein(s).