ArticleProceedings of the National Academy of Sciences of the United States of America2019
Prion protein quantification in human cerebrospinal fluid as a tool for prion disease drug development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- PrP turnover in vivo and the time to effect of prion disease therapeutics.PLoS pathogens · 2026Article
- Involvement of the spleen in the anti-prion activity of hydroxypropyl methylcellulose in mice.Scientific reports · 2026Article
- Prion protein (PrP) profiles in blood and CSF: insights into pre-symptomatic and symptomatic prion disease.Brain communications · 2026Article
- Prion protein fragment (106-126) activates NLRP3 inflammasome and promotes platelet-monocyte/neutrophil interactions, potentially contributing to an inflammatory state.Frontiers in cell and developmental biology · 2025Article
- Biological Fluid Biomarkers in Human Prion Diseases with a Note on Biosafety.Sub-cellular biochemistry · 2025Review
- Benchtop IR Imaging of Live Cells: Monitoring the Total Mass of Biomolecules in Single Cells.Analytical chemistry · 2024Article
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- Biomarker changes preceding symptom onset in genetic prion disease.medRxiv : the preprint server for health sciences · 2023Article
- A single-cell map of antisense oligonucleotide activity in the brain.Nucleic acids research · 2023Article
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- A single-cell map of antisense oligonucleotide activity in the brain.bioRxiv : the preprint server for biology · 2023Article
- Uncovering the universality of self-replication in protein aggregation and its link to disease.Science advances · 2022Article
- Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD.Nature communications · 2022Article
- Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS.JCI insight · 2022Article
- Genetic aspects of human prion diseases.Frontiers in neurology · 2022Review
- Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.Science advances · 2021Article
- TREM2 expression in the brain and biological fluids in prion diseases.Acta neuropathologica · 2021Article
- Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease.The Lancet. Neurology · 2021Review
- Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS.Acta neuropathologica communications · 2020Article
- Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 6 countries.
Funding
Abstract
Reduction of native prion protein (PrP) levels in the brain is an attractive strategy for the treatment or prevention of human prion disease. Clinical development of any PrP-reducing therapeutic will require an appropriate pharmacodynamic biomarker: a practical and robust method for quantifying PrP, and reliably demonstrating its reduction in the central nervous system (CNS) of a living patient. Here we evaluate the potential of ELISA-based quantification of human PrP in human cerebrospinal fluid (CSF) to serve as a biomarker for PrP-reducing therapeutics. We show that CSF PrP is highly sensitive to plastic adsorption during handling and storage, but its loss can be minimized by the addition of detergent. We find that blood contamination does not affect CSF PrP levels, and that CSF PrP and hemoglobin are uncorrelated, together suggesting that CSF PrP is CNS derived, supporting its relevance for monitoring the tissue of interest and in keeping with high PrP abundance in brain relative to blood. In a cohort with controlled sample handling, CSF PrP exhibits good within-subject test-retest reliability (mean coefficient of variation, 13% in samples collected 8-11 wk apart), a sufficiently stable baseline to allow therapeutically meaningful reductions in brain PrP to be readily detected in CSF. Together, these findings supply a method for monitoring the effect of a PrP-reducing drug in the CNS, and will facilitate development of prion disease therapeutics with this mechanism of action.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.