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Role of Cellular Prion Protein in the Amyloid-β Oligomer Pathophysiology of Alzheimer’s Disease

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Prions and Diseases

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Abstract

Alzheimer’s disease (AD) is the most common form of dementia affecting millions worldwide. The primary histopathological features of AD are amyloid-beta (Aβ) plaques and neurofibrillary tangles. Aβ oligomers (Aβo) are believed to be essential mediators of the synaptotoxicity and cell death that are characteristic of this illness. For decades, the exact mechanism for how Aβ exerted its toxic effect remained unknown. Recently, it has been shown that the cellular Prion Protein (PrPC) acts as a high-affinity binding partner for Aβo. Moreover, it has been demonstrated that PrPC is necessary for memory loss, impaired long-term potentiation, and neuronal dysfunction in transgenic mouse models of AD. Antagonizing PrPC in AD mouse models has also been shown to reverse memory deficits, so targeting PrPC is a potential avenue for treatment. This chapter will review the evidence connecting PrPC to Aβo pathophysiology.

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Author information

Authors and Affiliations

  1. Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology and Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA

    Adam C. Kaufman

  2. Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology and Department of Neurobiology, Yale University School of Medicine, 295 Congress Ave, New Haven, CT, 06536, USA

    Stephen M. Strittmatter M.D., Ph.D.

Authors
  1. Adam C. Kaufman
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  2. Stephen M. Strittmatter M.D., Ph.D.
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Correspondence to Stephen M. Strittmatter M.D., Ph.D. .

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Editors and Affiliations

  1. , Department of Pathology, Case Western Reserve University School o, 2085 Adelbert Road, Cleveland, 44106, Ohio, USA

    Wen-Quan Zou

  2. , Department of Neuropathology, Case Western Reserve University School o, 2085 Adelbert Road, Cleveland, 44106, Ohio, USA

    Pierluigi Gambetti

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Kaufman, A.C., Strittmatter, S.M. (2013). Role of Cellular Prion Protein in the Amyloid-β Oligomer Pathophysiology of Alzheimer’s Disease. In: Zou, WQ., Gambetti, P. (eds) Prions and Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5305-5_3

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