Figure 6.

Proposed pre-conversion IPD patterns of biomarker change for fast and slow IPDs. Each stage features expected intensities in PrP-amyloid seeding activity, neurodegeneration markers and clinical aspects, along with ancillary investigations known to herald the onset of conversion (neuropsychometry, and neurophysiology in P102L). Naturally, the small numbers in this study precludes the provision of precise quantitative scales at the present time. (A) Slow IPDs are likely to have an extended window for neurodegenerative markers, making it easier to capture and follow at 6–12 monthly sampling intervals; however, we only have partially sensitive RT-QuIC seeding assays for slow IPDs. (B) Fast IPDs are likely to have a very short and explosive neurodegeneration window, which means it might not be easy to capture and follow at similar sampling intervals; this may be offset by the existence of highly sensitive RT-QuIC assays (E200K only) that may become positive several years before clinical onset. The changes in CSF PrP amyloid seeding are hypothetical, current evidence is limited to a very small number of individuals and samples.