Details

Autor(en) / Beteiligte

• Thompson, Andrew G.B.
• Mead, Simon H.

Titel

Review: Fluid biomarkers in the human prion diseases

Ist Teil von

• Molecular and cellular neuroscience, 2019-06, Vol.97, p.81-92

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• The 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. •There are highly sensitive and specific CSF biomarkers for diagnosis of sporadic CJD.•The RT-QuIC assay has been an important advance in molecular diagnosis.•Several tests that can detect variant CJD infection in blood have now been reported.•Brain-derived proteins measured in blood, such as tau and NfL, show great potential.•Beyond diagnosis, these and other biomarkers may be valuable for clinical trials.