Neuronal RNA in relation to Alz-50 immunoreactivity in Alzheimer's disease

Both defective nucleic acid metabolism/protein synthesis and the expression of an abnormal antigen recognized by the Alz-50 antibody may be involved in the neuronal degeneration of Alzheimer's disease (AD). A multiparametric analysis involving Alz-50 immunocytochemistry and azure B--RNA microdensitometry was developed to compare nucleic acid alterations in Alz-50-positive neurons to those in Alz-50-negative neurons of the brain of AD patients. Alz-50-immunoreactive neurons of the hippocampal endplate (Rose's H3-H5 fields) and the subiculum exhibited significantly lower (by approximately 30%) total RNA contents than negative neurons of the corresponding region. The mean RNA content of Alz-50-positive neurons of the AD brain was also reduced in comparison to that of Alz-50-negative neurons of age-matched, nondemented controls, whereas there were no significant differences between negative neurons of AD patients and controls. The hippocampus of nondemented controls was also found to contain Alz-50-immunoreactive neurons, although 20- to 30-fold fewer than the hippocampus of AD patients. In the controls, there was also a tendency toward reduced RNA levels in Alz-50-positive versus -negative neurons. These data suggest a relationship between Alz-50 immunoreactivity and defective nucleic acid metabolism in the AD brain.