Co-existence of PrPD types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics

• Published in: Scientific reports Vol. 10; no. 1; p. 1503
• Main Authors: Cali, Ignazio, Puoti, Gianfranco, Smucny, Jason, Curtiss, Paul Michael, Cracco, Laura, Kitamoto, Tetsuyuki, Occhipinti, Rossana, Cohen, Mark Lloyd, Appleby, Brian Stephen, Gambetti, Pierluigi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.01.2020; Nature Publishing Group
• Subjects: 59; 631/337/470/460; 692/699/375/1937; 82; 82/29; 82/51; Bovine spongiform encephalopathy; Creutzfeldt-Jakob disease; Electrophoretic mobility; Homozygosity; Humanities and Social Sciences; Methionine; multidisciplinary; Prion protein; Science; Science (multidisciplinary); Valine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58446-0

We report a detailed study of a cohort of sporadic Creutzfeldt-Jakob disease (sCJD) VV1–2 type-mixed cases (valine homozygosity at codon 129 of the prion protein, PrP, gene harboring disease-related PrP, PrP D , types 1 and 2). Overall, sCJDVV1–2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrP D type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrP D type exceeded 20–25%. Overall, original features of types 1 (T1) and 2 (T2) in sCJDVV1 and -VV2, including rostrocaudal relative distribution and conformational indicators, were maintained in sCJDVV1–2 except for one of the two components of T1 identified by electrophoretic mobility as T1 21 . The T1 21 conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrP D T2 on T1 21 . The prevalence of sCJDVV1–2 was 23% or 57% of all sCJDVV cases, depending on whether standard or highly sensitive type-detecting procedures were adopted. This study, together with previous data from sCJDMM1–2 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD variants as an important component of sCJD, which cannot be identified with current non-tissue based diagnostic tests of prion disease.