Altered levels of amyloid protein precursor transcripts in the basal forebrain of behaviorally impaired aged rats

The beta/A4 protein is a constituent of plaque and vascular amyloid deposits in Alzheimer disease. Previous studies have shown increased levels of amyloid protein precursor (APP) mRNA in basal forebrain neurons in the disease. Morphological and neurochemical changes occur within the forebrain in Alzheimer disease and are also correlated with behavioral impairments in aged rats. Recent studies suggest that decreased nerve growth factor responsiveness of basal forebrain neurons is a feature of normal aging and of Alzheimer disease. We have used in situ hybridization to show that the abundance of specific forms of APP mRNA, which contain an inserted Kunitz-type serine protease inhibitor motif (APP-751, APP-770, and APP-related 563), are increased relative to the noninserted form (APP-695) of APP mRNA in the basal forebrain of aged rats. This increase appears to be specific to animals who exhibit spatial memory deficits but not aged rats without behavioral impairments.