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Conformationally altered p53: a novel Alzheimer's disease marker?

Molecular Psychiatry volume 13, pages 641–647 (2008)Cite this article

Abstract

The identification of biological markers of Alzheimer's disease (AD) can be extremely useful to improve diagnostic accuracy and/or to monitor the efficacy of putative therapies. In this regard, peripheral cells may be of great importance, because of their easy accessibility. After subjects were grouped according to diagnosis, the expression of conformationally mutant p53 in blood cells was compared by immunoprecipitation or by a cytofluorimetric assay. In total, 104 patients with AD, 92 age-matched controls, 15 patients with Parkinson's disease and 9 with other types of dementia were analyzed. Two independent methods to evaluate the differential expression of a conformational mutant p53 were developed. Mononuclear cells were analyzed by immunoprecipitation or by flow-cytometric analysis, following incubation with a conformation-specific p53 antibody, which discriminates unfolded p53 tertiary structure. Mononuclear cells from AD patients express a higher amount of mutant-like p53 compared to non-AD subjects, thus supporting the study of conformational mutant p53 as a new putative marker to discriminate AD from non-AD patients. We also observed a strong positive correlation between the expression of p53 and the age of patients. The expression of p53 was independent from the length of illness and from the Mini Mental State Examination value.

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Acknowledgements

This work was supported by the contribution of grants from the Ministry of University and Research (Grant no. 2005051707 to SG, MM and 2005054147 to DU), the Ministry of Health (progetto Alzheimer to ES), Fondo Ateneo Ricerca (University of Pavia to MR), ‘Progetto Giovani Ricercatori’ (University of Pavia to CL) and the Polish research ordered grant PBZ-KBN-124/P05/2004. J Kuznicki received an academic grant from the Foundation for Polish Research. We thank F Benvenuto for the initial suggestions in flow-cytometric experiments.

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Authors and Affiliations

  1. Department of Experimental and Applied Pharmacology, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy

    C Lanni, M Racchi & S Govoni

  2. Department of Animal Biology, IGM-CNR, Histochemistry and Cytometry, University of Pavia, Pavia, Italy

    G Mazzini

  3. Department of Geriatric Medicine, Ospedale S Orsola Fatebenefratelli, Brescia, Italy

    A Ranzenigo & R Polotti

  4. Laboratory of Neuropsychology, IRCCS Fondazione ‘Casimiro Mondino’, Pavia, Italy

    E Sinforiani

  5. Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy

    L Olivari, M Memo & D Uberti

  6. Medical Research Center Polish Academy of Science, Warszawa, Poland

    M Barcikowska & M Styczynska

  7. Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warszawa, Poland

    J Kuznicki & A Szybinska

  8. Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland

    J Kuznicki

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  1. C Lanni
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  2. M Racchi
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  3. G Mazzini
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  4. A Ranzenigo
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  7. L Olivari
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  8. M Barcikowska
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  9. M Styczynska
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  10. J Kuznicki
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  11. A Szybinska
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  12. S Govoni
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  13. M Memo
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  14. D Uberti
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Correspondence to C Lanni.

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Lanni, C., Racchi, M., Mazzini, G. et al. Conformationally altered p53: a novel Alzheimer's disease marker?. Mol Psychiatry 13, 641–647 (2008). https://doi.org/10.1038/sj.mp.4002060

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  • DOI: https://doi.org/10.1038/sj.mp.4002060

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