Production of the Alzheimer amyloid beta protein by normal proteolytic processing

Science. 1992 Oct 2;258(5079):126-9. doi: 10.1126/science.1439760.


The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.

Publication types

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

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Base Sequence
  • Cell Line
  • Immunoblotting
  • Leukemia, Myeloid / metabolism*
  • Molecular Sequence Data
  • Neuroblastoma / metabolism*
  • Transfection


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor