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Clioquinol decreases amyloid-β burden and reduces working memory impairment in a transgenic mouse model of alzheimer's disease

Grossi, Cristina, Francese, Simona, Casini, Angela, Rosi, Maria Cristina, Luccarini, Ilaria, Fiorentini, Anna, Gabbiani, Chiara, Messori, Luigi, Moneti, Gloriano and Casamenti, Fiorella 2009. Clioquinol decreases amyloid-β burden and reduces working memory impairment in a transgenic mouse model of alzheimer's disease. Journal of Alzheimer's Disease 17 (2) , pp. 423-440. 10.3233/JAD-2009-1063

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Abstract

Clioquinol (CQ) is a "metal protein attenuating compound" that crosses the blood-brain barrier and binds, with high affinity, copper(II) and zinc(II), two metal ions critically involved in amyloid-β aggregation and toxicity. CQ was recently proposed for the treatment of Alzheimer's disease, but controversial data have been reported so far concerning its real therapeutic advantages. We describe here results of chronic CQ treatment in the TgCRND8 mouse model of Alzheimer's disease. Remarkably, based on classical behavioral tests, CQ treatment was found to revert, to a large extent, the working memory impairments that are characteristic of this mouse model. Pairwise, a significant reduction of amyloid-β plaque burden, both in the cortex and in the hippocampus, was detected as well as an attenuation of astrogliosis. MALDI Mass Spectrometry Imaging technique revealed a specific localization of CQ in the above mentioned brain areas. Modest but significant effects on the absolute and relative brain concentrations of the three most important biometals (i.e., copper, zinc, and iron) were highlighted following CQ treatment. The pharmacological and mechanistic implications of the above findings are thoroughly discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
R Medicine > R Medicine (General)
Publisher: IOS Press
Date of Acceptance: 20 December 2008
Last Modified: 04 Jun 2017 08:30
URI: http://orca.cf.ac.uk/id/eprint/79357

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