Fig. 3

Candidate markers of neuropathology in carrier and control CSF. CSF a T-tau and b NfL levels were measured by ELISA for N = 39 participants who have made at least one study visit, for whom genotypes were available at time of analysis, and where appropriate CSF aliquots were available. For each participant included, samples were taken from the most recent visit at time of analysis. Symptomatic prion disease CSF samples (red, N = 24 for T-tau, N = 19 for NfL) were included from both sporadic and E200K genetic prion disease. The operator was masked to mutation status. Dots represent means, and line segments 95% confidence intervals, of measurements within dynamic range with 2 technical replicates each. c, d For N = 10 participants who had completed a longitudinal visit ≥ 10 months after their first visit, both T-tau and NfL were measured by ELISA across all visits to assess longitudinal dynamics. As in Fig. 1b, CSF from the following three timepoints is represented for each participant: initial visit, 2–4-month follow-up visit (the 2–4-month follow-up visit was missing for N = 1 participant in c and d), and 10–20-month follow-up visit. e–g RT-QuIC was performed on CSF from 39 participants who made at least one study visit. For each participant, samples were taken from the most recent visit at time of analysis. RT-QuIC was performed following an established protocol for second-generation CSF RT-QuIC using SHaPrP substrate [24]. Reactions were seeded with 20 μL CSF from N = 26 symptomatic prion disease cases (e) and N = 39 MGH study participants, including 16 mutation-negative (f) and 23 asymptomatic mutation-positive (g) with each reaction run in quadruplicate. Kinetic curves—normalized thioflavin T (ThT) fluorescence (y axis) vs. time in hours (x axis)—are shown for each sample, averaged across four replicates