Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues

Michael K. Lee, Hilda H. Slunt, Lee J. Martin, Gopal Thinakaran, Grace Kim, Samuel E. Gandy, Mary Seeger, Edward Koo, Donald L. Price, Sangram S. Sisodia

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as ~28 kDa N-terminal and ~18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somato- dendritic and neuropil compartments.

Original languageEnglish (US)
Pages (from-to)7513-7525
Number of pages13
JournalJournal of Neuroscience
Volume16
Issue number23
DOIs
StatePublished - Dec 1 1996

Keywords

  • Alzheimer's disease
  • development
  • immunocytochemistry
  • mRNA expression
  • presenilins
  • protein accumulation

ASJC Scopus subject areas

  • Neuroscience(all)

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