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Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease.

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-beta 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 reverse, to a large extent, the working memory impairments that are characteristic of this mouse model. Pairwise, a significant reduction of amyloid-beta 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.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, University of Florence, Florence, Italy.

    , , , , , , , ,

    Source

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Analysis of Variance
    Animals
    Body Weight
    Cerebral Cortex
    Clioquinol
    Disease Models, Animal
    Glial Fibrillary Acidic Protein
    Hippocampus
    Humans
    Maze Learning
    Memory Disorders
    Memory, Short-Term
    Metals
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Reaction Time
    Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19363260

    Citation

    Grossi, Cristina, et al. "Clioquinol Decreases Amyloid-beta Burden and Reduces Working Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 17, no. 2, 2009, pp. 423-40.
    Grossi C, Francese S, Casini A, et al. Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2009;17(2):423-40.
    Grossi, C., Francese, S., Casini, A., Rosi, M. C., Luccarini, I., Fiorentini, A., ... Casamenti, F. (2009). Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 17(2), pp. 423-40. doi:10.3233/JAD-2009-1063.
    Grossi C, et al. Clioquinol Decreases Amyloid-beta Burden and Reduces Working Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2009;17(2):423-40. PubMed PMID: 19363260.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. AU - Grossi,Cristina, AU - Francese,Simona, AU - Casini,Angela, AU - Rosi,Maria Cristina, AU - Luccarini,Ilaria, AU - Fiorentini,Anna, AU - Gabbiani,Chiara, AU - Messori,Luigi, AU - Moneti,Gloriano, AU - Casamenti,Fiorella, PY - 2009/4/14/entrez PY - 2009/4/14/pubmed PY - 2009/12/17/medline SP - 423 EP - 40 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 17 IS - 2 N2 - 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-beta 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 reverse, to a large extent, the working memory impairments that are characteristic of this mouse model. Pairwise, a significant reduction of amyloid-beta 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/19363260/Clioquinol_decreases_amyloid_beta_burden_and_reduces_working_memory_impairment_in_a_transgenic_mouse_model_of_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=17&issue=2&spage=423 DB - PRIME DP - Unbound Medicine ER -