Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads

Area of Science:

• Neuroscience
• Infectious Diseases
• Biochemistry

Background:

• Prion diseases are fatal, transmissible neurodegenerative disorders.
• Prions are present in body fluids like blood, but at very low concentrations.
• Current diagnostic tests for prions in blood often lack sensitivity, leading to false negatives.

Purpose of the Study:

• To develop a method for concentrating prions from large volumes of blood plasma.
• To improve the sensitivity of prion detection assays for early diagnosis.
• To validate a new assay for quantifying prion infectivity.

Main Methods:

• Utilized beads conjugated to positively charged peptoids for prion capture.
• Tested the capture efficiency of peptoid beads using plasma from prion-infected hamsters.
• Assessed prion infectivity by transmitting captured prions to indicator mice.
• Validated the peptoid-based misfolded protein assay (MPA) against in vivo prion infectivity.

Main Results:

• Peptoid-conjugated beads successfully captured PrP aggregates from infected hamster plasma.
• Captured prions retained infectivity in both symptomatic and preclinical disease stages.
• The peptoid-based misfolded protein assay (MPA) readout strongly correlated with in vivo prion infectivity.
• Demonstrated efficient disease transmission to mice via bead-captured prions.

Conclusions:

• Quantitative preanalytical prion enrichment using peptoid beads significantly enhances assay sensitivity.
• The MPA serves as a reliable, sensitive, and quantitative surrogate for prion infectivity.
• This method holds promise for sensitive prion detection in plasma for research and diagnostics.