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Choroid plexus implants rescue Alzheimer’s disease-like pathologies by modulating amyloid-β degradation

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Abstract

The choroid plexuses (CP) release numerous biologically active enzymes and neurotrophic factors, and contain a subpopulation of neural progenitor cells providing the capacity to proliferate and differentiate into other types of cells. These characteristics make CP epithelial cells (CPECs) excellent candidates for cell therapy aiming at restoring brain tissue in neurodegenerative illnesses, including Alzheimer’s disease (AD). In the present study, using in vitro approaches, we demonstrated that CP were able to diminish amyloid-β (Aβ) levels in cell cultures, reducing Aβ-induced neurotoxicity. For in vivo studies, CPECs were transplanted into the brain of the APP/PS1 murine model of AD that exhibits advanced Aβ accumulation and memory impairment. Brain examination after cell implantation revealed a significant reduction in brain Aβ deposits, hyperphosphorylation of tau, and astrocytic reactivity. Remarkably, the transplantation of CPECs was accompanied by a total behavioral recovery in APP/PS1 mice, improving spatial and non-spatial memory. These findings reinforce the neuroprotective potential of CPECs and the use of cell therapies as useful tools in AD.

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Acknowledgments

This work was supported by grants from Instituto de Salud Carlos III (FIS 09-01636), Fundación Investigación Médica Mutua Madrileña (2008/93; 2010/0004), Fundación Ramón Areces, Ministerio de Educación y Ciencia (SAF2010-15558), and CIBERNED (BESAD-P.2010). We thank Isabel Sastre for technical assistance, and Agnieszka Krzyzanowska, PhD, for the careful revision of this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Av. de Córdoba s/n, 28041, Madrid, Spain

    Marta Bolos, Desireé Antequera & Eva Carro

  2. Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain

    Marta Bolos, Desireé Antequera, Jesús Aldudo, María Jesús Bullido & Eva Carro

  3. Centro de Biología Molecular Severo Ochoa, CBM (UAM/CSIC), Madrid, Spain

    Jesús Aldudo, Henrike Kristen & María Jesús Bullido

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  1. Marta Bolos
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  2. Desireé Antequera
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  5. María Jesús Bullido
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  6. Eva Carro
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Correspondence to Eva Carro.

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Bolos, M., Antequera, D., Aldudo, J. et al. Choroid plexus implants rescue Alzheimer’s disease-like pathologies by modulating amyloid-β degradation. Cell. Mol. Life Sci. 71, 2947–2955 (2014). https://doi.org/10.1007/s00018-013-1529-4

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  • DOI: https://doi.org/10.1007/s00018-013-1529-4

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