Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report

• Published in: Journal of medical case reports Vol. 6; no. 1; p. 348
• Main Authors: Rodríguez-Martínez, Ana B, López de Munain, Adolfo, Ferrer, Isidro, Zarranz, Juan J, Atarés, Begoña, Villagra, Nuria T, Arteagoitia, Jose M, Garrido, Joseba M, Juste, Ramón A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11-10-2012; BioMed Central; BMC
• Subjects: Analysis; Case Report; Case studies; Codon; Creutzfeldt-Jakob disease; Creutzfeldt–Jakob; Depression, Mental; Diagnosis; Physiological aspects; Prion; Prions; Protease resistance; Proteases; Resistant PrP; Sensitive PrP; Variably Protease Sensitive Prionopathy
• ISSN: 1752-1947; 1752-1947
• DOI: 10.1186/1752-1947-6-348

The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported.
A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.Neuropathological findings showed: spongiform change in the patient's cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous.
Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.