Decreased alpha-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer's disease

Nat Med. 1995 Aug;1(8):829-32. doi: 10.1038/nm0895-829.


The neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular plaques and intracellular neurofibrillary tangles. A constituent of senile plaques in AD is beta-amyloid, a hydrophobic peptide of 39-43 amino acids and a fragment of the amyloid precursor protein (APP). APP can be metabolized by at least two pathways, one of which involves generation of soluble APP by an unidentified enzyme named alpha-secretase. This cleavage generates alpha-secretase-cleaved, soluble APP (alpha-sAPP), which in this investigation was measured by a new assay in cerebrospinal fluid (CSF) from members of a Swedish AD family with a pathogenic mutation at APP670/671 (ref. 2). Family members who carry the mutation and are diagnosed with AD had low levels of alpha-sAPP (160 +/- 48 ng ml-1), with no overlap compared with non-carriers (257 +/- 48 ng ml-1). Carriers of the presymptomatic mutation showed intermediate alpha-sAPP levels. Today there exists no antemortem marker in AD with sufficient sensitivity and specificity, but measurement of alpha-sAPP represents a new and promising diagnostic marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / immunology
  • Amyloid beta-Protein Precursor / metabolism*
  • Aspartic Acid Endopeptidases
  • Biomarkers / cerebrospinal fluid
  • Blotting, Western
  • Endopeptidases / metabolism*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Sweden / epidemiology


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Peptide Fragments
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human