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¹ Department of Neurology, Philipps-University Marburg, 35039 Marburg, Germany
² Laboratory of Medicinal Chemistry, ³ Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders, The Feinstein Institute for Medical Research, Manhasset, NY 11030
⁴ Institute of Neuropathology, University Hospital Muenster, 48149 Muenster, Germany
⁵ Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697
⁶ Department of Behavioural Biology, University of Muenster, 48149 Muenster, Germany
⁷ Institute of Clinical Psychology and Psychotherapy, Technical University Dresden, 01187 Dresden, Germany
⁸ Department of Neurology, University of Bonn, 53105 Bonn, Germany

CORRESPONDENCE Yousef Al-Abed:yalabed{at}nshs.edu

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 guanylhydrazone 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 significantly 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 significant dose-dependent 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.

© 2008 Bacher et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• 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 Ass production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease. JCB 182: i1-i1 [Full Text]  

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