A 70-year-old man develops progressive dementia with visuospatial impairment, personality change, and cortical blindness. Autopsy shows spongiform vacuolation, neuronal loss, and gliosis in the cortex without inflammation, and the disease was transmissible to chimpanzees. The fundamental mechanism of prion disease involves:
- A Conformational change of normal cellular PrPC to misfolded PrPSc that acts as a template to convert further PrPC ✓
- B Viral integration into neuronal DNA causing progressive neurodegeneration
- C Autoimmune NMDAR antibody-mediated neuronal destruction
- D Mitochondrial dysfunction from somatic mtDNA mutations
Correct answer: A. Conformational change of normal cellular PrPC to misfolded PrPSc that acts as a template to convert further PrPC
Explanation
Prion diseases (spongiform encephalopathies) are caused by misfolded PrPSc (scrapie isoform), which differs from normal PrPC only in conformation (predominantly beta-sheet vs. alpha-helix). PrPSc acts as a template, binding to and converting normal PrPC to PrPSc in an exponential chain reaction — propagating without nucleic acids. This 'protein-only' hypothesis explains transmissibility without conventional virus. Spongiform vacuolation, gliosis, and absence of inflammation are pathological hallmarks. Creutzfeldt-Jakob disease (CJD) fits this clinical description.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.