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Activity-Dependent Neuroprotective Protein (ADNP) Expression in the Amyloid Precursor Protein/Presenilin 1 Mouse Model of Alzheimer’s Disease

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Abstract

A major determinant in the pathogenesis of Alzheimer’s disease (AD) is the deposition of β-amyloid (Aβ) peptides in specific areas of the central nervous system. Therefore, animal models of Alzheimer amyloidosis are excellent tools to identify candidates to facilitate drug screening and to understand the molecular pathology of AD. Activity-dependent neuroprotective protein (ADNP) plays an essential role in brain development, and NAP (NAPVSIPQ, generic name: davunetide)—a peptide derived from ADNP—is currently in clinical development for the treatment of neurodegenerative disorders. However, the link between ADNP expression and AD remains unexplored. To test whether ADNP is affected by the onset of AD and progression, we employed the PS1xAPP mouse model (PS1M146L × APP751SL transgenic mice) to analyze the mRNA expression of ADNP in the hippocampus and cerebellum in early and advanced stages of disease. Results showed that ADNP expression in 6-month-old PS1xAPP mice hippocampus was higher than in wild-type (WT) mice. ADNP was originally identified as a vasoactive intestinal peptide (VIP)-responsive gene taking part in the VIP-mediated neurotrophic pathway. Interestingly, the expression of VIP was not affected in the same experimental setting, suggesting that ADNP expression is a VIP-independent marker associated with AD. Moreover, in the cerebellum, a brain area not affected by Aβ deposition, ADNP mRNA expression in 6-month-old PS1xAPP and WT were not different. A similar extent of hippocampal ADNP expression was observed in 18-month-old WT and PS1xAPP mice, in contrast to the differential expression level at 6 months of age. However, hippocampal ADNP expression in both WT and PS1xAPP was increased with aging similar to VIP mRNA expression. Our findings support the hypothesis that ADNP expression is related to early or mild AD progression by a VIP-independent mechanism.

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Acknowledgements

This work was partially supported by grants from the Spanish Ministry of Health (PI052056 and PI061641 to D.P.; PI060567 to J.V.; PI060556 to A.G.). The D.P. laboratory is part of the national cooperative research network in multiple sclerosis RETIC-REEM, Spanish Ministry of Health. M.T., A.G., and J.V. are part of the Network Centre for Biomedical Research on Neurodegenerative Diseases (CIBERNED).

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Authors and Affiliations

  1. CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine (CSIC-University of Seville–UPO-Junta de Andalucía), Americo Vespucio Ave, Parque Científico y Tecnológico Cartuja 93, 41092, Seville, Spain

    Rafael Fernandez-Montesinos & David Pozo

  2. IBiS-Seville Biomedical Research Institute (Hospital Universitario Virgen del Rocío–CSIC-University of Seville–Junta de Andalucía) and Network Centre for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Seville, Spain

    Manuel Torres & Javier Vitorica

  3. Department of Cell Biology, Genetics and Physiology, University of Malaga and Network Centre for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Malaga, Spain

    David Baglietto-Vargas & Antonia Gutierrez

  4. The Adams Super-Center for Brain Studies and Levi-Edersheim-Gitter Institute, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Illana Gozes

Authors
  1. Rafael Fernandez-Montesinos
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  2. Manuel Torres
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  3. David Baglietto-Vargas
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  4. Antonia Gutierrez
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  5. Illana Gozes
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  6. Javier Vitorica
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  7. David Pozo
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Corresponding author

Correspondence to David Pozo.

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Rafael Fernandez-Montesinos and Manuel Torres contributed equally to this work.

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Fernandez-Montesinos, R., Torres, M., Baglietto-Vargas, D. et al. Activity-Dependent Neuroprotective Protein (ADNP) Expression in the Amyloid Precursor Protein/Presenilin 1 Mouse Model of Alzheimer’s Disease. J Mol Neurosci 41, 114–120 (2010). https://doi.org/10.1007/s12031-009-9300-x

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  • DOI: https://doi.org/10.1007/s12031-009-9300-x

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