Relation of Neuronal APP-751/APP-695 mRNA Ratio and Neuritic Plaque Density in Alzheimer's Disease

Abstract

An ongoing controversy concerns the cellular distribution of the differentially spliced forms of the amyloid protein precursor (APP) mRNAs and changes in prevalence of these transcripts during Alzheimer's disease. In situ hybridization on serial sections was used to prove that most hippocampal pyramidal neurons contain both APP-751 and APP-695 mRNA species. The APP-751/APP-695 mRNA ratio is generally increased during Alzheimer's disease, as shown by RNA gel blot analysis. Moreover, there was a strong linear relation between the increase in APP-751/APP-695 mRNA ratio in pyramidal neurons and the density of senile plaques within the hippocampus and entorhinal cortex. Thus, the increase in APP-751/APP-695 mRNA provides a molecular marker for regional variations in plaque density between individuals diagnosed with Alzheimer's disease by the commonly used composite criteria.