CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease

Michael Bacher, Richard Dodel, Bayan Aljabari, Kathy Keyvani, Philippe Marambaud, Rakez Kayed, Charles Glabe, Nicole Goertz, Anne Hoppmann, Norbert Sachser, Jens Klotsche, Susanne Schnell, Lars Lewejohann, Yousef Al-Abed

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide " oligomers " and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent gua-nylhydrazone with established antiinflammatory properties, interferes with Aβ assembly and protects neuronal cells from the toxic effect of soluble Aβ oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk signif cantly reduced Aβ deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a signif cant dosedependent decrease of total Aβ accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD.

Original languageEnglish (US)
Pages (from-to)1593-1599
Number of pages7
JournalJournal of Experimental Medicine
Volume205
Issue number7
DOIs
StatePublished - Jul 7 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Bacher, M., Dodel, R., Aljabari, B., Keyvani, K., Marambaud, P., Kayed, R., Glabe, C., Goertz, N., Hoppmann, A., Sachser, N., Klotsche, J., Schnell, S., Lewejohann, L., & Al-Abed, Y. (2008). CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease. Journal of Experimental Medicine, 205(7), 1593-1599. https://doi.org/10.1084/jem.20060467