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Oxidative stress damage and oxidative stress responses in the choroid plexus in Alzheimer’s disease

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Abstract

Choroid plexus homogenates from 27 cases with Alzheimer disease-related pathology (AD), stages I/0 (n = 5), III–IV/0-B (n = 15) and V–VI/B-C (n = 7) and 3 age-matched controls (no clinical symptoms, no neuropathological lesions) were processed for gel electrophoresis and western blotting for oxidation markers carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL). Increased CEL and CML expression was seen in AD cases stages IVB, and V–VI/B-C when compared to controls and cases with AD-related pathology classified as I/0 and III/0. Variable stress damage was seen in stage III/B. Although lower stages of AD did not show β-amyloid deposition in the choroid plexus, the amount of β-amyloid was very variable at stages V/VI as revealed by western blotting, suggesting that other factors in addition to local fibrillar β-amyloid were associated with oxidative damage in the choroid plexus. Two-dimensional gel electrophoresis and western blotting to CEL and CML in combination with mass spectrometry disclosed increased intensity of variable spots in AD cases leading to the identification of tyrosine 3/tryptophan 5-monooxygenase activation protein, zeta polypeptide, tropomyosin 3 isoform, and apolipoprotein A-II (ApoA-II) as targets of increased oxidative damage in AD. Oxidation of these proteins may result in impaired protein interactions, protein folding and protein kinase activity; abnormal function of endothelial and vascular smooth muscle cells; and impaired HDL-cholesterol metabolism in the choroid plexus in advanced stages of AD.

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Acknowledgments

This work was funded by grant PI08/0582 from the Spanish Ministry of Health, Carlos III Institute of Health. We thank Maria Antonia Odena and Eliandre Oliveira of the Proteomics Platform, Barcelona Science Park, for mass spectrometry study; and T. Yohannan for editorial help.

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Authors and Affiliations

  1. Servei Anatomia Patològica, Institut Neuropatologia, CIBERNED, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Universitat de Barcelona, Carrer Feixa LLarga sn, 08907, Barcelona, Spain

    Ester Perez-Gracia, Rosa Blanco, Margarita Carmona & Isidro Ferrer

  2. Neuroscience Laboratory, Research Center, Hospital 12 de Octubre, CIBERNED, Madrid, Spain

    Eva Carro

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  1. Ester Perez-Gracia
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  2. Rosa Blanco
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  3. Margarita Carmona
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  4. Eva Carro
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  5. Isidro Ferrer
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Correspondence to Isidro Ferrer.

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Perez-Gracia, E., Blanco, R., Carmona, M. et al. Oxidative stress damage and oxidative stress responses in the choroid plexus in Alzheimer’s disease. Acta Neuropathol 118, 497–504 (2009). https://doi.org/10.1007/s00401-009-0574-4

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  • DOI: https://doi.org/10.1007/s00401-009-0574-4

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