Differential Expression of Three Types of Amyloid Protein Precursor mRNA in Alzheimer’s Disease Brain
Deposition of amyloid β-protein in senile plaque cores and cerebral vessels is one of the characteristic findings in Alzheimer’s disease brain. Complementary DNA (cDNA) encoding the precursor of amyloid β-protein (APP695) was cloned and sequenced1. The precursor has structural features characteristic of cell surface receptors. We cloned APP cDNAs from a cDNA library of a human glioblastoma cell line, and found two more cDNAs encoding APPs (APP751 and APP770) together with APP695 cDNA previously reported2. APP751 has a 56 amino-acid insert, and APP770 has an additional 19 amino-acid insert (Fig. 1). These two inserts are encoded by exons, 7 and 8 2,3, respectively. APP gene exists as a single copy, indicating that the three types of APP mRNA are produced by alternative splicing from a common transcript. The amino-acid sequence encoded by exon 7 is highly homologous to the basic trypsin inhibitor family. The fact that this APP fragment has actually a protease inhibitor activity was shown by an in vitro expression experimeht2.
KeywordsHuman Glioblastoma Cell Line Common Transcript Amyloid Protein Precursor mRNA Protease Inhibitor Domain pSP64 Plasmid
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