• Thompson Andrew G B AGB MRC Prion Unit at University College London (UCL), UCL Institute of Prion Diseases, UCL, London W1W 7FF, United Kingdom of Great Britain and North and Simon H Mead.
• MRC Prion Unit at University College London (UCL), UCL Institute of Prion Diseases, UCL, London W1W 7FF, United Kingdom of Great Britain and Northern Ireland.
• Mol. Cell. Neurosci. 2019 Jun 1; 97: 81-92.

AbstractThe human prion diseases are a diverse set of often rapidly progressive neurodegenerative conditions associated with abnormal forms of the prion protein. We review work to establish diagnostic biomarkers and assays that might fill other important roles, particularly those that could assist the planning and interpretation of clinical trials. The field now benefits from highly sensitive and specific diagnostic biomarkers using cerebrospinal fluid: detecting by-products of rapid neurodegeneration or specific functional properties of abnormal prion protein, with the second generation real time quaking induced conversion (RT-QuIC) assay being particularly promising. Blood has been a more challenging analyte, but has now also yielded valuable biomarkers. Blood-based assays have been developed with the potential to screen for variant Creutzfeldt-Jakob disease, although it remains uncertain whether these will ever be used in practice. The very rapid neurodegeneration of prion disease results in strong signals from surrogate protein markers in the blood that reflect neuronal, axonal, synaptic or glial pathology in the brain: notably the tau and neurofilament light chain proteins. We discuss early evidence that such tests, applied alongside robust diagnostic biomarkers, may have potential to add value as clinical trial outcome measures, predictors of future disease course (including for asymptomatic individuals at high risk of prion disease), and as rapidly accessible and sensitive markers to aid early diagnosis.Copyright © 2018. Published by Elsevier Inc.

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