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Accumulation of prion protein in the brain that is not associated with transmissible disease

Pedro Piccardo1, Jean C Manson, Declan King

  • 1Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 16, 2007
PubMed

Insights

Prion diseases involve prion protein (PrP) accumulation. This study found that PrP amyloid plaques in familial prion disease do not always indicate infectivity or cause spongiform encephalopathy.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Prion diseases, or transmissible spongiform encephalopathies, are characterized by prion protein (PrP) accumulation, with pathological PrP isoforms (PrPSc) serving as diagnostic markers.
  • The relationship between specific PrP forms and infectivity remains unclear, necessitating further investigation into their roles in disease pathogenesis.

Purpose of the Study:

  • To investigate the association between different forms of prion protein (PrP) accumulation and infectivity in familial prion disease.
  • To determine if PrP amyloid deposition is a reliable indicator of transmissible spongiform encephalopathy infectivity.

Main Methods:

  • Bioassays were conducted using human brain extracts from two distinct familial Gerstmann-Sträussler-Scheinker P102L prion disease cases.
  • Transgenic mice (Tg PrP101LL) were inoculated with brain tissue, and disease transmission, spongiform degeneration, and PrP deposition patterns were analyzed.

Main Results:

  • Tissue from a case with spongiform degeneration efficiently transmitted disease to mice, causing spongiform encephalopathy.
  • Tissue from a case without spongiform degeneration showed minimal disease transmission but significant PrP-amyloid deposition in recipient mice.
  • Subsequent passages in mice confirmed the absence of neurological disease transmission from the amyloid-depositing tissue, despite persistent PrP-amyloid accumulation.

Conclusions:

  • PrP amyloidogenesis may occur independently of spongiform encephalopathy and prion disease infectivity.
  • PrP amyloid deposition might not be a reliable marker for transmissible spongiform encephalopathy infectivity.
  • An infectious agent could promote amyloid formation without causing disease, or be sequestered within plaques, rendering it non-pathogenic.

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