CU ZN SUPEROXIDE-DISMUTASE IN PATIENTS WITH NONFAMILIAL ALZHEIMERS-DISEASE/

Chromosome 21 contains genes whose altered expression has long been as sociated with Down's syndrome and whose altered structure with some ca ses of Alzheimer's disease (AD). The gene for the Cu/Zn superoxide dis mutase enzyme (SOD-1), a key enzyme in the metabolism of oxygen free r adicals, is located on the distal portion of chromosome 21. Due to the triplication of the SOD-1 gene, patients with Down's syndrome have an almost 50% increase in their SOD activity. On the other hand, almost 25% of the patients with Down's syndrome over 40 years of age develop progressive dementia, with clinical symptoms of AD. Therefore, we deci ded to evaluate whether abnormalities in the production of free radica ls could be detected in blood cells from AD patients, and whether they correlated with molecular variations in the Cu/Zn SOD-1 gene. Superox ide anion production was evaluated spectrophotometrically in suspensio ns of monocytes from 9 sporadic AD patients, and from 9 aged-matched a pparently normal controls. After stimulation with increasing concentra tions of n-formyl-methionyl-leucyl-phenylalanine (fMLP) or Ca ionophor e A23187, monocyte free radical generation was quantitatively, and qua litatively normal. Furthermore, restriction fragment length polymorphi sm (RFLP) analysis of leukocyte DNA digested with a variety of enzymes , gave comparable results in patients and controls. Our data support t he possibility that in addition to the generation of free radicals, ot her directions should be explored to elucidate the mechanisms of demen tia in AD.