Vallabh SM et al. 2024, Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion (Neurology 103(2):e209506, PMID 38896810, doi 10.1212/wnl.0000000000209506)

A brief report in Neurology (2024) from a team at Massachusetts General Hospital and the Broad Institute. It follows a single-center cohort of asymptomatic people at risk for genetic prion disease, plus controls, with roughly yearly CSF and plasma sampling, and describes marker behaviour in the few who developed symptoms. The main result is that CSF RT-QuIC seeding activity appeared before onset in E200K carriers, while neuronal-damage markers were weak predictors and CSF PrP stayed stable. All findings here are aggregate cohort results.

Key facts

  • The report lists 17 authors led by Sonia Vallabh, with Eric Minikel and Steven Arnold among them; it appeared online on 2024-06-19 and in the 2024-07-23 issue of Neurology (vol 103, issue 2, e209506).
  • The cohort had 41 pathogenic-variant carriers and 21 controls, all asymptomatic at entry, seen about yearly between July 2017 and February 2023.
  • Four carriers became symptomatic during follow-up (three E200K, one P102L); no control or other carrier did.
  • Three E200K carriers who converted had CSF RT-QuIC seeding activity before onset, with windows of about 1 year in a codon 129 V/V case and about 2.5 and 3.1 years in two M/V cases; the P102L converter stayed RT-QuIC negative.
  • Plasma NfL rose in all four converters but stayed inside the range seen in nonconverters and controls; plasma GFAP and CSF NfL, T-tau and beta-synuclein rose in only about half, and none reliably separated converters relative to age or personal baseline.
  • CSF PrP differed between people and was lower in carriers, but was stable within a person for up to six years (mean variability about 9%), including at RT-QuIC-positive timepoints.
  • The authors note limits: only four onsets, an E200K skew, COVID-era missed visits, standard RT-QuIC conditions only, and no imaging or newer sample types.
  • Funding named in the paper: BroadIgnite Accelerator, Ionis Pharmaceuticals, Prion Alliance, the CJD Foundation and NIH (record lists NIA P30 AG062421). The paper is open access.

Timeline

  1. 2017Cohort follow-up described in the paper begins (study window July 2017 to February 2023).
  2. 2024Manuscript received by Neurology.
  3. 2024Accepted.
  4. 2024Published online.
  5. 2024Appears in the print issue (Neurology 103(2)).

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Last checked 1 November 2026

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