Presenilin-1-dependent transcriptome changes

Károly Mirnics, Zeljka Korade, Dominique Arion, Orly Lazarov, Travis Unger, Melissa Macioce, Michael Sabatini, David Terrano, Katherine C. Douglass, Nina F. Schor, Sangram S. Sisodia

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Familial forms of Alzheimer's disease (FADs) are caused by the expression of mutant presenilin 1 (PS1) or presenilin 2. Using DNA microarrays, we explored the brain transcription profiles of mice with conditional knock-out of PS1 (cKO PS1) in the forebrain. In parallel, we performed a transcription profiling of the hippocampus and frontal cortex of the FAD-linked ΔE9 mutant transgenic (TG) mice and matched controls [TG mice expressing wild-type human PS1 (hPS1)]. When the TG and cKO datasets were cross-compared, the majority of the 30 common expression alterations were in opposite direction, suggesting that the FAD-linked PS1 variant produces transcriptome changes primarily by gain of aberrant function. Our microarray studies also revealed an unanticipated inverse correlation of transcript levels between the brains of mice that coexpress ΔE9 hPS1+ amyloid precursor protein (APP)695 Swe and ΔE9 hPS1 single transgenic mice. The opposite directionality of these changes in transcript levels must be a function of APP and/or APP derivatives.

Original languageEnglish (US)
Pages (from-to)1571-1578
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number6
DOIs
StatePublished - Feb 9 2005

Keywords

  • Alzheimer's disease
  • Animal model
  • DNA microarray
  • Gene expression
  • Presenilin
  • Transcriptome

ASJC Scopus subject areas

  • Neuroscience(all)

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    Mirnics, K., Korade, Z., Arion, D., Lazarov, O., Unger, T., Macioce, M., Sabatini, M., Terrano, D., Douglass, K. C., Schor, N. F., & Sisodia, S. S. (2005). Presenilin-1-dependent transcriptome changes. Journal of Neuroscience, 25(6), 1571-1578. https://doi.org/10.1523/JNEUROSCI.4145-04.2005