The Neuropathology Core plays a critical role in this Program Project by providing detailed histopathological characterization of a large number of animal and human tissues, utilizing several techniques.
In Specific Aim 1, the Core has the task of determining the presence, type, severity and anatomic distribution of the structural lesions, along with the topography and pattern of deposition of the scrapie prion protein (PrPSc) in brains from mice and hamsters. Brains will be sectioned according to precise and fixed coordinates and processed for histological and immunohistochemical examinations. If required, other tissues will be similarly processed. Highly specialized services such as lesion profiling and PET blot and histoblot will also be provided. Altogether, these techniques allow for the establishment of the histopathological phenotype, and are designed to assure that data can be compared.
Specific Aim 2 is directed at acquiring and characterizing brain tissues from human prion diseases needed for the coordinated studies of Research Projects 1 and 3. The Core will take advantage of the unique opportunity of acquiring the rare cases needed from the tissue collection of the National Prion Disease Pathology Surveillance Center (NPDPSC), led by the Core Director. The third objective of the Core is to report the results of tissue examinations to the Project Leaders and store processed tissue samples, which will remain available to the members of the Program Project. The qualifications of the Core Director, the variety and consistency of the examinations and access to a unique tissue collection make the Neuropathology Core essential to the success of the entire Program Project. Project

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-RWM-M (S3))
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Case Western Reserve University
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Shannon, Matthew D; Theint, Theint; Mukhopadhyay, Dwaipayan et al. (2018) Conformational Dynamics in the Core of Human Y145Stop Prion Protein Amyloid Probed by Relaxation Dispersion NMR. Chemphyschem :
Kim, Chae; Xiao, Xiangzhu; Chen, Shugui et al. (2018) Artificial strain of human prions created in vitro. Nat Commun 9:2166
Notari, Silvio; Appleby, Brian S; Gambetti, Pierluigi (2018) Variably protease-sensitive prionopathy. Handb Clin Neurol 153:175-190
Diaz-Espinoza, R; Morales, R; Concha-Marambio, L et al. (2018) Treatment with a non-toxic, self-replicating anti-prion delays or prevents prion disease in vivo. Mol Psychiatry 23:777-788
Cali, Ignazio; Cohen, Mark L; Haik, Stephane et al. (2018) Iatrogenic Creutzfeldt-Jakob disease with Amyloid-? pathology: an international study. Acta Neuropathol Commun 6:5
Theint, Theint; Xia, Yongjie; Nadaud, Philippe S et al. (2018) Structural Studies of Amyloid Fibrils by Paramagnetic Solid-State Nuclear Magnetic Resonance Spectroscopy. J Am Chem Soc 140:13161-13166
Cracco, Laura; Appleby, Brian S; Gambetti, Pierluigi (2018) Fatal familial insomnia and sporadic fatal insomnia. Handb Clin Neurol 153:271-299
Li, Qiuye; Wang, Fei; Xiao, Xiangzhu et al. (2018) Structural attributes of mammalian prion infectivity: Insights from studies with synthetic prions. J Biol Chem 293:18494-18503
Aucoin, Darryl; Xia, Yongjie; Theint, Theint et al. (2018) Protein-solvent interfaces in human Y145Stop prion protein amyloid fibrils probed by paramagnetic solid-state NMR spectroscopy. J Struct Biol :
Theint, Theint; Nadaud, Philippe S; Aucoin, Darryl et al. (2017) Species-dependent structural polymorphism of Y145Stop prion protein amyloid revealed by solid-state NMR spectroscopy. Nat Commun 8:753

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