A Novel Combination of Prion Strain Co-Occurrence in Patients with Sporadic Creutzfeldt-Jakob Disease

Atsushi Kobayashi, Yasushi Iwasaki, Masaki Takao, Yuko Saito, Toru Iwaki, Zechen Qi, Ryouta Torimoto, Taishi Shimazaki, Yoshiko Munesue, Norikazu Isoda, Hirofumi Sawa, Keisuke Aoshima, Takashi Kimura, Hinako Kondo, Shirou Mohri, Tetsuyuki Kitamoto

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Abstract

Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathologic features, genotype at polymorphic codon 129 [methionine (M)/valine (V)] of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathologic features and the coexistence of two types of abnormal prion proteins in the same patient also have been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathologic characteristics of the MM2 thalamic form (ie, neuronal loss of the inferior olivary nucleus of the medulla). Furthermore, coexistence of biochemical features of the MM2 thalamic form also was confirmed in the identified cases. In addition, in transmission experiments using prion protein–humanized mice, the brain material from the identified case showed weak infectivity and generated characteristic abnormal prion proteins in the inoculated mice resembling those after inoculation with brain material of MM2 thalamic form. Taken together, these results show that the co-occurrence of MM1 and MM2 thalamic form is a novel entity of sporadic Creutzfeldt-Jakob disease prion strain co-occurrence. The present study raises the possibility that the co-occurrence of the MM2 thalamic form might have been overlooked so far because of the scarcity of abnormal prion protein accumulation and restricted neuropathology.

Original languageEnglish
Pages (from-to)1276-1283
Number of pages8
JournalAmerican Journal of Pathology
Volume189
Issue number6
DOIs
Publication statusPublished - Jun 2019

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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    Kobayashi, A., Iwasaki, Y., Takao, M., Saito, Y., Iwaki, T., Qi, Z., Torimoto, R., Shimazaki, T., Munesue, Y., Isoda, N., Sawa, H., Aoshima, K., Kimura, T., Kondo, H., Mohri, S., & Kitamoto, T. (2019). A Novel Combination of Prion Strain Co-Occurrence in Patients with Sporadic Creutzfeldt-Jakob Disease. American Journal of Pathology, 189(6), 1276-1283. https://doi.org/10.1016/j.ajpath.2019.02.012