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The Three Glycotypes in the London Classification System of Sporadic Creutzfeldt-Jakob Disease Differ in Disease Duration

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Abstract

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of CJD and is believed to be caused by the misfolding and aggregation of endogenous prion protein. Several classification systems have been developed to correlate the molecular characteristics of these misfolded prions (PrPSc) to the heterogeneous clinical presentations of sCJD. A central component of these systems is glycotyping, which involves the interpretation of the results of western immunoblotting of the protease-resistant fragment of the misfolded prion protein (PrPres). The two main classification systems differ in their recognition of a unique banding pattern on electrophoretic gels correlating to a putative clinical subtype. The perpetuation of both classification systems within scientific literature is, in part, due to a paucity of high-level evidence that conclusively addresses the merit of recognising each unique banding pattern. Here, 110 post-mortem confirmed cases of sCJD collected at the Australian Creutzfeldt-Jakob Disease Registry (ANCJDR) between 1993 and 2018 were analysed and classified as per the London classification system. The data presented here demonstrated that sCJD cases with ‘type 1′ and ‘type 2′ PrPSc as defined by the London classification system differ in their disease duration. No other differences in clinical phenotype or biological characteristics were found to be statistically significant. These findings highlight the importance of sample size and replicability in analyses of this rare disease process. Recognising these glycotypes as phenotypically distinct may represent ‘best practice’ in the collection and processing of sCJD samples within international registries for research purposes.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Availability of Data and Materials

Please find supplementary information attached. Raw data is stored securely at the Australian National Creutzfeldt-Jakob Disease Registry.

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Acknowledgements

The authors gratefully acknowledge the support and generosity from the Luscombe family, Suzanne Solvyns and the CJD Support Group Network Australia.

Funding

Creutzfeldt-Jakob Disease Support Group Network Memorial Award in memory of Michael Luscombe. The role of this funding source was solely to purchase testing kits and had no role in the study design, collection, analysis or interpretation of data, or writing of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

B.N. analysed data and wrote the manuscript. D.E. analysed data and supervised students. V.L. performed experiments and analysed data. L.N. analysed data. Q-X.L. performed experiments and analysed data. C.S. analysed data and supervised students. S.C. analysed data and supervised students. D.V. analysed data and supervised students.

Corresponding author

Correspondence to Blair Ney.

Ethics declarations

Ethics Approval

Data collection and storage was mediated through the Australian National Creutzfeldt-Jakob Disease Registry as per routine operations. Ethical approval for use of this data was gained through the University of Melbourne (Ethics ID: 1341074) and conforms with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to Participate

Obtaining informed consent to participate is part of routine operations at the ANCJDR. Written informed consent to participate in research derived from ANCJDR operations was gained from all patients in this study, or where patients cannot provide informed consent, from the appropriate next of kin and/or legal decision-maker.

Consent for Publication

Obtaining informed consent to publish patient data is also part of routine operations at the ANCJDR. The authors affirm that written informed consent for publication of patient data derived from ANCJDR operations was also gained from all patients in this study, or where patients cannot provide informed consent, from the appropriate next of kin and/or legal decision-maker.

Competing Interests

The authors declare no competing interests.

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Ney, B., Eratne, D., Lewis, V. et al. The Three Glycotypes in the London Classification System of Sporadic Creutzfeldt-Jakob Disease Differ in Disease Duration. Mol Neurobiol 58, 3983–3991 (2021). https://doi.org/10.1007/s12035-021-02396-9

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  • DOI: https://doi.org/10.1007/s12035-021-02396-9

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