Exogenous seeding of cerebral β-amyloid deposition in βAPP-transgenic rats

Authors

  • Rebecca F. Rosen,

    1. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author
    • These authors contributed equally.

  • Jason J. Fritz,

    1. Department of Neurology, Emory University, Atlanta, Georgia, USA
    2. Center for Neurodegenerative Disease, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author
    • These authors contributed equally.

  • Jeromy Dooyema,

    1. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author
  • Amarallys F. Cintron,

    1. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author
  • Tsuyoshi Hamaguchi,

    1. Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
    Search for more papers by this author
  • James J. Lah,

    1. Department of Neurology, Emory University, Atlanta, Georgia, USA
    2. Center for Neurodegenerative Disease, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author
  • Harry LeVine III,

    1. Sanders-Brown Center on Aging, Department of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA
    Search for more papers by this author
  • Mathias Jucker,

    1. Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
    Search for more papers by this author
  • Lary C. Walker

    1. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA
    2. Department of Neurology, Emory University, Atlanta, Georgia, USA
    3. Center for Neurodegenerative Disease, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author

Address correspondence and reprint requests to Lary Walker, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA. E-mail: lary.walker@emory.edu

Abstract

J. Neurochem. (2012) 120, 660–666.

Abstract

Deposition of the amyloid-β (Aβ) peptide in senile plaques and cerebral Aβ angiopathy (CAA) can be stimulated in Aβ-precursor protein (APP)-transgenic mice by the intracerebral injection of dilute brain extracts containing aggregated Aβ seeds. Growing evidence implicates a prion-like mechanism of corruptive protein templating in this phenomenon, in which aggregated Aβ itself is the seed. Unlike prion disease, which can be induced de novo in animals that are unlikely to spontaneously develop the disease, previous experiments with Aβ seeding have employed animal models that, as they age, eventually will generate Aβ lesions in the absence of seeding. In the present study, we first established that a transgenic rat model expressing human APP (APP21 line) does not manifest endogenous deposits of Aβ within the course of its median lifespan (30 months). Next, we injected 3-month-old APP21 rats intrahippocampally with dilute Alzheimer brain extracts containing aggregated Aβ. After a 9-month incubation period, these rats had developed senile plaques and CAA in the injected hippocampus, whereas control rats remained free of such lesions. These findings underscore the co-dependence of agent and host in governing seeded protein aggregation, and show that cerebral Aβ-amyloidosis can be induced even in animals that are relatively refractory to the spontaneous origination of parenchymal and vascular deposits of Aβ.

Ancillary