Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

Nature. 1988 Feb 11;331(6156):530-2. doi: 10.1038/331530a0.

Abstract

Alzheimer's disease is characterized by cerebral deposits of amyloid beta-protein (AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225-nucleotide insert. The sequence of the 56 amino acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism.

Publication types

  • Comparative Study

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid / genetics*
  • Amyloid beta-Protein Precursor
  • Base Sequence
  • Brain / embryology
  • Brain Chemistry
  • DNA / genetics
  • DNA, Recombinant
  • Down Syndrome / genetics
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Protease Inhibitors / genetics*
  • Protein Precursors / genetics*
  • RNA Splicing
  • Sequence Homology, Nucleic Acid
  • Trypsin Inhibitors / genetics
  • Tumor Cells, Cultured / analysis

Substances

  • Amyloid
  • Amyloid beta-Protein Precursor
  • DNA, Recombinant
  • Protease Inhibitors
  • Protein Precursors
  • Trypsin Inhibitors
  • DNA

Associated data

  • GENBANK/X06981