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Updated: Jan 28, 2026

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Variably protease-sensitive prionopathy mimicking frontotemporal dementia.

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Neuropathology : Official Journal of the Japanese Society of Neuropathology
|March 9, 2019
PubMed
Summary

Variably protease-sensitive prionopathy (VPSPr) is a rare prion disease that can mimic frontotemporal dementia (FTD). Diagnosis requires prion protein (PrP) testing, even in elderly patients with atypical symptoms.

Keywords:
Creutzfeldt-Jakob diseaseprion diseasesprion proteinprionsvariably protease-sensitive prionopathy

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Area of Science:

  • Neurology
  • Neurodegenerative Diseases
  • Prion Biology

Background:

  • Sporadic prion diseases are fatal neurodegenerative disorders.
  • Variably protease-sensitive prionopathy (VPSPr) is a recently identified sporadic human prion disorder.
  • VPSPr can present with atypical and lengthy clinical histories, mimicking other neurodegenerative conditions like frontotemporal dementia (FTD).

Observation:

  • A case of VPSPr is described in a 61-year-old man with a long history of suspected FTD.
  • The patient presented with speech and movement abnormalities, later developing swallowing difficulties.
  • Brain examination revealed atrophy, spongiform microvacuolation, and prion protein (PrP) deposits, with minimal Alzheimer pathology.

Findings:

  • Histological analysis showed patchy spongiform changes and PrP microplaques.
  • Western blotting confirmed a low molecular weight protease-resistant PrP band characteristic of VPSPr.
  • Diagnostic features included PrP immunohistochemistry and Western blotting, excluding other common neurodegenerative pathologies.

Implications:

  • VPSPr diagnosis necessitates specific prion protein (PrP) immunohistochemistry and Western blotting.
  • Patchy spongiform changes, especially in the absence of other pathologies, should raise suspicion for VPSPr.
  • This case highlights the importance of considering VPSPr in elderly patients with prolonged, atypical neurodegenerative presentations.