TY - JOUR
T1 - A Novel Combination of Prion Strain Co-Occurrence in Patients with Sporadic Creutzfeldt-Jakob Disease
AU - Kobayashi, Atsushi
AU - Iwasaki, Yasushi
AU - Takao, Masaki
AU - Saito, Yuko
AU - Iwaki, Toru
AU - Qi, Zechen
AU - Torimoto, Ryouta
AU - Shimazaki, Taishi
AU - Munesue, Yoshiko
AU - Isoda, Norikazu
AU - Sawa, Hirofumi
AU - Aoshima, Keisuke
AU - Kimura, Takashi
AU - Kondo, Hinako
AU - Mohri, Shirou
AU - Kitamoto, Tetsuyuki
N1 - Funding Information:
Supported by Japan Society for the Promotion of Science KAKENHI grants 18K05963 (A.K.) and 18K06506 (M.T.); a grant from the Ichiro Kanehara Foundation (A.K.); a grant from the Suhara Memorial Foundation (A.K.); a grant from The Kato Memorial Trust for Nambyo Research (A.K.); the Research Committee of Prion Disease and Slow Virus Infection, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health and Labour Sciences Research grants, the Ministry of Health, Labour and Welfare, Japan (M.T.); and Japan Agency for Medical Research and Development grant JP18dm0107103 (Y.S.). Supported by Japan Society for the Promotion of Science KAKENHI grants 18K05963 (A.K.) and 18K06506 (M.T.); a grant from the Ichiro Kanehara Foundation (A.K.); a grant from the Suhara Memorial Foundation (A.K.); a grant from The Kato Memorial Trust for Nambyo Research (A.K.); the Research Committee of Prion Disease and Slow Virus Infection, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health and Labour Sciences Research grants, the Ministry of Health, Labour and Welfare, Japan (M.T.); and Japan Agency for Medical Research and Development grant JP18dm0107103 (Y.S.). We thank members of the Creutzfeldt-Jakob Disease Surveillance Committee in Japan, Creutzfeldt-Jakob disease specialists in the prefectures, and Creutzfeldt-Jakob disease patients and families for providing important clinical information; Hiroko Kudo, Miyuki Yamamoto, and Ayumi Yamazaki for their excellent technical assistance; and Brent Bell for critical review of the manuscript. Supported by Japan Society for the Promotion of Science KAKENHI grants 18K05963 (A.K.) and 18K06506 (M.T.); a grant from the Ichiro Kanehara Foundation (A.K.); a grant from the Suhara Memorial Foundation (A.K.); a grant from The Kato Memorial Trust for Nambyo Research (A.K.); the Research Committee of Prion Disease and Slow Virus Infection, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health and Labour Sciences Research grants, the Ministry of Health, Labour and Welfare, Japan (M.T.); and Japan Agency for Medical Research and Development grant JP18dm0107103 (Y.S.).
Publisher Copyright:
© 2019 American Society for Investigative Pathology
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2019.02.012
DO - 10.1016/j.ajpath.2019.02.012
M3 - Article
C2 - 30926338
AN - SCOPUS:85065614688
VL - 189
SP - 1276
EP - 1283
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -