Creutzfeldt-Jakob disease (CJD), the most common human prion disorder, may occur as "pure" neurodegeneration with isolated prion deposits in the brain tissue; however, comorbid cases with different concomitant neurodegenerative diseases have been reported. This retrospective study examined correlations of clinical, neuropathological, molecular-genetic, immunological, and neuroimaging biomarkers in pure and comorbid CJD. A total of 215 patients have been diagnosed with CJD during the last ten years by the Czech National Center for Prion Disorder Surveillance. Data were collected from all patients with respect to diagnostic criteria for probable CJD, including clinical description, EEG, MRI, and CSF findings. A detailed neuropathological analysis uncovered that only 11.16% were "pure" CJD, while 62.79% had comorbid tauopathy, 20.47% had Alzheimer's disease, 3.26% had frontotemporal lobar degeneration, and 2.33% had synucleinopathy. The comorbid subgroup analysis revealed that tauopathy was linked to putaminal hyperintensity on MRIs, and AD mainly impacted the age of onset, hippocampal atrophy on MRIs, and beta-amyloid levels in the CSF. The retrospective data analysis found a surprisingly high proportion of comorbid neuropathologies; only 11% of cases were verified as "pure" CJD, i.e., lacking hallmarks of other neurodegenerations. Comorbid neuropathologies can impact disease manifestation and can complicate the clinical diagnosis of CJD.

• Keywords
• Alzheimer’s disease, Creutzfeldt–Jakob disease, MRI, beta-amyloid, comorbid neuropathology, tauopathy,
• Publication type
• Journal Article MeSH

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a hereditary neurodegenerative disease characterized by extracellular aggregations of pathological prion protein (PrP) forming characteristic plaques. Our study aimed to evaluate the micromorphology and protein composition of these plaques in relation to age, disease duration, and co-expression of other pathogenic proteins related to other neurodegenerations. Hippocampal regions of nine clinically, neuropathologically, and genetically confirmed GSS subjects were investigated using immunohistochemistry and multichannel confocal fluorescent microscopy. Most pathognomic prion protein plaques were small (2-10 µm), condensed, globous, and did not contain any of the other investigated proteinaceous components, particularly dystrophic neurites. Equally rare (in two cases out of nine) were plaques over 50 µm having predominantly fibrillar structure and exhibit the presence of dystrophic neuritic structures; in one case, the plaques also included bulbous dystrophic neurites. Co-expression with hyperphosphorylated protein tau protein or amyloid beta-peptide (Aβ) in GSS PrP plaques is generally a rare observation, even in cases with comorbid neuropathology. The dominant picture of the GSS brain is small, condensed plaques, often multicentric, while presence of dystrophic neuritic changes accumulating hyperphosphorylated protein tau or Aβ in the PrP plaques are rare and, thus, their presence probably constitutes a trivial observation without any relationship to GSS development and progression.

• Keywords
• Gerstmann–Sträussler–Scheinker syndrome, PrP, co-expression, plaques,
• MeSH
• Adult MeSH
• Gerstmann-Straussler-Scheinker Disease * genetics   metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation, Missense * MeSH
• Protein Aggregation, Pathological * genetics   metabolism   pathology   MeSH
• Prion Proteins * genetics   metabolism   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Prion Proteins * MeSH