A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors

Nature. 1988 Feb 11;331(6156):525-7. doi: 10.1038/331525a0.


The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta-protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid / genetics*
  • Amyloid beta-Protein Precursor
  • Base Sequence
  • Brain Chemistry
  • DNA / genetics
  • DNA, Recombinant
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Protease Inhibitors / genetics*
  • Protein Precursors / genetics*
  • RNA, Messenger / genetics*
  • Receptors, Cell Surface
  • Sequence Homology, Nucleic Acid
  • Serine Proteinase Inhibitors*
  • Tumor Cells, Cultured / analysis


  • Amyloid
  • Amyloid beta-Protein Precursor
  • DNA, Recombinant
  • Protease Inhibitors
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Cell Surface
  • Serine Proteinase Inhibitors
  • DNA

Associated data

  • GENBANK/X06989
  • GENBANK/Y00297