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

Meng Qi Xia, Oksana Berezovska, Tae Wan Kim, Wei Ming Xia, Andrew Liao, Rudolph E. Tanzi, Dennis Selkoe, Bradley T. Hyman

Research output: Contribution to journalReview article

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalJournal of the Neurological Sciences
Volume158
Issue number1
DOIs
StatePublished - Jun 11 1998

Keywords

  • AD
  • Flow cytometry
  • Human brain
  • Immunohistochemistry
  • Immunoprecipitation
  • Plaque
  • Presenilins
  • Tangle

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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