Preclinical biomarkers of prion infection and neurodegeneration. (April 2020)

• Record Type: Journal Article
• Authors: Mok, Tze How; Mead, Simon
• Is Part Of: Current opinion in neurobiology. Volume 61(2020)
• Page Start: 82
• Page End: 88
• Publication Date: 2020-04
• Subjects: Neurobiology -- Periodicals; 573.8
• DOI: 10.1016/j.conb.2020.01.009
• Languages: English
• ISSNs: 0959-4388

Abstract

Highlights: Preclinical biomarkers are crucial for drug study design and timing of therapy in neurodegenerative diseases. Animal models of prion disease show a long clinically silent period prior to onset despite high prion titres. The RT-QuIC assay is a highly sensitive and specific prion seeding assay but use is unclear in preclinical stage. Downstream protein markers of neurodegeneration are also very useful after diagnosis. Rate of change rather than absolute biomarker value may be a more sensitive measure. Abstract : 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.