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

Ignazio Cali, Gianfranco Puoti, Jason Smucny, Paul Michael Curtiss, Laura Cracco, Tetsuyuki Kitamoto, Rossana Occhipinti, Mark Lloyd Cohen, Brian Stephen Appleby, Pierluigi Gambetti

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5 Citations (Scopus)


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, PrPD, types 1 and 2). Overall, sCJDVV1–2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrPD type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrPD 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 T121. The T121 conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrPD T2 on T121. 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.

Original languageEnglish
Article number1503
JournalScientific reports
Issue number1
Publication statusPublished - 2020 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General

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