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Are prions transported by plasma exosomes?

Larisa Cervenakova1, Paula Saá1, Oksana Yakovleva2

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Misfolded prion protein (PrP(TSE)) was detected in plasma extracellular vesicles (EVs) from infected mice. Only EVs amplified by Protein Misfolding Cyclic Amplification (PMCA) transmitted disease, confirming EVs as potential prion carriers.

Keywords:
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Area of Science:

  • Neuroscience
  • Biochemistry
  • Infectious Diseases

Background:

  • Transmissible spongiform encephalopathy (TSE) agents cause prion diseases.
  • Misfolded prion protein (PrP(TSE)) is detectable in blood of infected individuals.
  • Extracellular vesicles (EVs), including exosomes, are implicated in disease transmission.

Purpose of the Study:

  • To detect PrP(TSE) in plasma EVs from mice infected with Gerstmann-Sträussler-Scheinker disease (Fukuoka-1 isolate).
  • To assess the infectivity of blood components and EVs in transmitting prion disease.
  • To confirm the efficacy of Protein Misfolding Cyclic Amplification (PMCA) in detecting infectious prions in EVs.

Main Methods:

  • Detection of PrP(TSE) in plasma EVs using PMCA.
  • Intracranial injection of blood components and EVs into Tga20 transgenic mice.
  • Assay of disease transmission from various blood fractions and amplified EVs.

Main Results:

  • PrP(TSE) was detected by PMCA in plasma EVs from Fukuoka-1 infected mice.
  • Only amplified plasma EVs containing PrP(TSE) and infected brain homogenate transmitted disease.
  • Plasma EVs without PMCA and blood cellular components failed to transmit prion disease.

Conclusions:

  • PMCA is highly sensitive for detecting PrP(TSE) in plasma EVs.
  • EVs, particularly exosomes, are efficient blood-borne carriers of infectious prions.
  • Further research is needed to elucidate the role of EVs in prion disease pathogenesis and transmission.