The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system

Neuron. 1995 Feb;14(2):467-75. doi: 10.1016/0896-6273(95)90302-x.


Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis 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 / metabolism
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / analysis*
  • Animals
  • Antibodies
  • Antibody Specificity
  • Blotting, Western
  • Brain / cytology*
  • Cattle
  • Humans
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis
  • Oligopeptides / immunology
  • Organ Specificity
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / analysis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Sequence Homology, Amino Acid
  • Synaptophysin / analysis*
  • Torpedo


  • Amyloid beta-Protein Precursor
  • Antibodies
  • Oligopeptides
  • Recombinant Proteins
  • Synaptophysin