title: Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.
abstract: Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA.
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D004247:DNA / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009693:Nucleic Acid Hybridization; D011480:Protease Inhibitors / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D015842:Serine Proteinase Inhibitors
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D011498:Protein Precursors; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D004247:DNA