BETA-A4-AMYLOID PROTEIN-PRECURSOR MESSENGER-RNA ISOFORMS WITHOUT EXON-15 ARE UBIQUITOUSLY EXPRESSED IN RAT-TISSUES INCLUDING BRAIN, BUT NOTIN NEURONS

The betaA4-amyloid protein precursor (APP), the source of the betaA4-a myloid deposits found in Alzheimer brains, constitutes a family of tra nsmembrane glycoproteins generated by alternative splicing. While exon 7 and exon 8 are well known to be alternatively spliced, APP mRNA iso forms without exon 15 were only recently identified in leukocytes and rat brain microglial cells and therefore denoted as L-APP mRNAs. In or der to perform a detailed analysis of individual L-APP mRNA isoforms i n perfused rat tissues, we developed a quantitative polymerase chain r eaction assay from reverse transcribed RNA allowing us to analyze the alternatively spliced region in between exon 6 and 16. In all peripher al tissues examined, L-APP mRNA isoforms were detected comprising betw een 25% (skeletal muscle) and about 70% (aorta, pancreas) of total APP transcripts. All four possible A.PP mRNA isoforms without exon 15 wer e shown to exist, i.e. L-APP752, L-APP733, L-APP696, and L-APP677. L-A PP expression in the central nervous system (approximately 4% of total APP mRNA) was then studied in more detail by analyzing different brai n regions and tissues and primary cultured brain cells. The only cell type which was shown not to express L-APP mRNA to a detectable level i s the neuronal cell. Ubiquitous expression of APP mRNAs lacking exon 1 5 except for neurons indicates an important function in non-neuronal c ells and is especially remarkable since neurons are the primarily affe cted cells in Alzheimer's disease.