Imipramine and citalopram facilitate amyloid precursor protein secretion in vitro

Magdolna Pákáski, Annamária Bjelik, Marietta Hugyecz, Péter Kása, Zoltán Janka, János Kálmán

Research output: Contribution to journalArticle

37 Citations (Scopus)


Comorbid depression of Alzheimer's disease (AD) is a common mood disorder in the elderly and a broad spectrum of antidepressants have been used for its treatment. Aβ peptides and other derivatives of the amyloid precursor protein (APP) have been implicated as central to the pathogenesis of AD. However, the functional relationship of APP and its proteolytic derivatives to antidepressant therapy is not known. In this study, Western blotting was used to test the ability of the tricyclic antidepressant (TCA) imipramine or the selective serotonin reuptake inhibitor (SSRI) citalopram to change the release of APP and the protein kinase C (PKC) content. Both antidepressants increased APP secretion in primary rat neuronal cultures. Imipramine or citalopram enhanced the level of secreted APP by 3.2- or 3.4-fold, respectively. Increases in PKC level were observed only after imipramine treatment. These in vitro data suggest that both TCA and SSRI are able to interfere with the APP metabolism. Imipramine promotes the non-amyloidogenic route of APP processing via stimulatory effects on PKC. We propose that PKC is not involved in the mechanism underlying the effects of citalopram on the APP metabolism. Since the secreted APP is not further available for the pathological cleavage of β- and γ-secretases, antidepressant medication might be beneficial in AD therapy.

Original languageEnglish
Pages (from-to)190-195
Number of pages6
JournalNeurochemistry international
Issue number3
Publication statusPublished - Aug 1 2005


  • APP
  • Alzheimer's disease
  • Antidepressant
  • Neuronal culture
  • PKC

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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