The Prion Atlas: Substrate, Detection, and Getting Someone to Order the Test

The Prion Atlas: Substrate, Detection, and Getting Someone to Order the Test. Monograph PRN-ATLAS-001, v2.2, 3 September 2026. Human prion diseases remain uniformly fatal. In a nucleated-polymerisation model the disease-free equilibrium is locally stable only when substrate M lies below M-star. Agents that reduce seed burden without holding M below that value can delay growth while they are present; they do not make the origin an attractor after withdrawal. This monograph writes the threshold explicitly, maps a three-lever protocol and its Monte Carlo failure modes onto it, and then scores the same protocol on a 12,000-draw human-timed clinic (EXP 24). For PRNP carriers, sampled blood volume still sets Poisson sensitivity. For sporadic disease the first loss is recognition. Paterson et al. reported 3.8 misdiagnoses and a mean 7.9 months to the correct name in a pathology-proven cohort. Applying that interval to every sporadic case is invalid for MM1 disease, whose clinical course is often about four months. At population prevalence, CSF RT-QuIC has a positive predictive value of 0.18 percent; after a crude rapidly progressive dementia flag the same assay has a PPV of 95 percent. Improving blood limit of detection without changing who is tested recovers no lead time in EXP 23. Among 9685 sporadic simulated patients who would have died untreated, a pasted 7.9-month lag yields a 16 percent firewall-cure fraction. A five-month US claims clock yields 26 percent. Diagnosis at two thirds of each patients own course yields 45 percent. A median 62-day RT-QuIC-era lag yields 63 percent. That 63 percent is not the MM1 number. EXP 26 puts MM1 at 49 percent on the same 62-day clock and at 21 percent if treatment waits 89 days from onset. EXP 27 splits that wait. Treating draws with diffusion restriction on the first MRI one week after first visit raises MM1 cure from 11 percent to 70 percent if the visit is 14 days after onset. The protocol is fixed across arms; the calendar and the strain mix are not. Percentages are fractions of simulated draws. No clinical-efficacy claim is made. Sequences and protocols are public domain. Text and analysis CC-BY 4.0. Artifacts CC0 1.0. Contact: jackson@email.zapdev.link