Lack of specific association of presenilin 1 (PS-1) protein with plaques and tangles in Alzheimer's disease

J Neurol Sci. 1998 Jun 11;158(1):15-23. doi: 10.1016/s0022-510x(98)00106-3.


Missense mutations in the presenilin-1 (PS-1) gene are causally related to the majority of familial early-onset Alzheimer's disease (FAD). PS-1 immunohistochemical expression in normal human brain and in brains with Alzheimer's disease (AD) has so far been controversial. Here, we report a study of PS-1 expression in brains, cell lines and peripheral blood mononuclear cells using a panel of well characterized PS-1-specific antibodies. These antibodies were characterized by immunofluorescent staining of PS-1 transfectants followed by flow cytometric analysis. In human brain, widespread neuronal staining was observed. PS-1 immunoreactivity was primarily confined to neuronal cell bodies and proximal dendrites. Weaker staining of microglia was also detected, in accord with the finding of PS-1 immunoreactivity in monocytes. PS-1 expression is not particularly associated with neurons either containing or spared from neurofibrillary tangles, nor with senile plaques. The level of PS-1 expression does not differ between normal and AD brains. Immunoprecipitation from AD, FAD and control brains revealed only a 32 kDa N-terminal fragment and an 18-20 kDa C-terminal fragment. Little or no full length PS-1 was detected. The enriched presence of PS-1 in neurons implies an important role in neuronal function, however, the lack of apparent association of its expression with AD pathology signifies the need for a better understanding of its pathophysiological role.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Astrocytoma / pathology
  • Blotting, Western
  • Brain Chemistry*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Glioma / pathology
  • Humans
  • Leukemia, Monocytic, Acute / pathology
  • Membrane Proteins / analysis*
  • Microglia / chemistry
  • Nerve Tissue Proteins / analysis*
  • Neurocytoma / pathology
  • Neurofibrillary Tangles / chemistry*
  • Neurons / chemistry
  • Plaque, Amyloid / chemistry*
  • Presenilin-1
  • Recombinant Fusion Proteins / analysis
  • Transfection
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Membrane Proteins
  • Nerve Tissue Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • Recombinant Fusion Proteins