Preclinical biomarkers of prion infection and neurodegeneration.

Tze How Mok, Simon Mead

Current opinion in neurobiology 2020 Apr

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Therapeutic strategies and study designs for neurodegenerative diseases have started to explore the potential of preventive treatment in healthy people, emphasising characterisation of biomarkers capable of indicating proximity to clinical onset. This need is even more pressing for individuals at risk of prion disease given its rarity which virtually precludes the probability of recruiting enough numbers for well powered preventive trials based on clinical endpoints. Experimental mouse inoculation studies have revealed a rapid exponential rise in infectious titres followed by a relative plateau of considerable duration before clinical onset. This clinically silent incubation period represents a potential window of opportunity for the adaptation of ultrasensitive prion seeding assays to define the onset of prion infection, and for neurodegenerative biomarker discovery through similarly sensitive digital immunoassay platforms. Copyright © 2020 Elsevier Ltd. All rights reserved.