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Open Access

Prion protein and Aβ‐related synaptic toxicity impairment

Anna Maria Calella, Mélissa Farinelli, Mario Nuvolone, Osvaldo Mirante, Rita Moos, Jeppe Falsig, Isabelle M. Mansuy, Adriano Aguzzi

Author Affiliations

  1. Anna Maria Calella1,,
  2. Mélissa Farinelli2,,
  3. Mario Nuvolone1,3,,
  4. Osvaldo Mirante2,
  5. Rita Moos1,
  6. Jeppe Falsig1,
  7. Isabelle M. Mansuy (mansuy{at}hifo.uzh.ch) *,2 and
  8. Adriano Aguzzi (adriano.aguzzi{at}usz.ch) *,1
  1. 1Institute of Neuropathology, University Hospital Zürich, Zürich, Switzerland
  2. 2Medical Faculty of the University of Zürich, Department of Biology, Brain Research Institute, Swiss Federal Institute of Technology, Zürich, Switzerland
  3. 3Department of Internal Medicine, Amyloid Center, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
  1. * Isabelle M. Mansuy, Tel: +41 44 635 33 60; Fax: +41 44 635 33 03

    Adriano Aguzzi, Tel: +41‐44‐255 2107; Fax: +41‐44 255 44 02

  1. These authors contributed equally to this work.

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Abstract

Alzheimer's disease (AD), the most common neurodegenerative disorder, goes along with extracellular amyloid‐β (Aβ) deposits. The cognitive decline observed during AD progression correlates with damaged spines, dendrites and synapses in hippocampus and cortex. Numerous studies have shown that Aβ oligomers, both synthetic and derived from cultures and AD brains, potently impair synaptic structure and functions. The cellular prion protein (PrPC) was proposed to mediate this effect. We report that ablation or overexpression of PrPC had no effect on the impairment of hippocampal synaptic plasticity in a transgenic model of AD. These findings challenge the role of PrPC as a mediator of Aβ toxicity.

See accompanying article: http://dx.doi.org/10.1002/emmm.2010000868.

  • Received May 18, 2010.
  • Revision received June 17, 2010.
  • Accepted June 21, 2010.

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