MM2-Thalamic Creutzfeldt-Jacob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain

F. Moda, S. Suardi, G. Di Fede, A. Indaco, L. Limido, C. Vimercati, M. Ruggerone, I. Campagnani, J.P.M. Langeveld, A. Terruzzi, A. Brambilla, P. Zerbi, P. Fociani, T. Bishop, G.W. Will, J.C. Manson, G. Giaccone, F. Tagliavini

Research output: Contribution to journalArticleAcademicpeer-review

41 Citations (Scopus)

Abstract

In CreutzfeldtJakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrPSc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrPSc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrPSc. Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrPSc, a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form.
Original languageEnglish
Pages (from-to)662-669
Number of pages8
JournalBrain Pathology
Volume22
Issue number5
DOIs
Publication statusPublished - 2012

Keywords

  • sporadic fatal insomnia
  • prpsc types
  • protein
  • variant
  • brain
  • classification
  • cooccurrence
  • degeneration
  • coexistence
  • scrapie

Fingerprint Dive into the research topics of 'MM2-Thalamic Creutzfeldt-Jacob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain'. Together they form a unique fingerprint.

  • Cite this

    Moda, F., Suardi, S., Di Fede, G., Indaco, A., Limido, L., Vimercati, C., Ruggerone, M., Campagnani, I., Langeveld, J. P. M., Terruzzi, A., Brambilla, A., Zerbi, P., Fociani, P., Bishop, T., Will, G. W., Manson, J. C., Giaccone, G., & Tagliavini, F. (2012). MM2-Thalamic Creutzfeldt-Jacob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain. Brain Pathology, 22(5), 662-669. https://doi.org/10.1111/j.1750-3639.2012.00572.x