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.

Department of Neurology 3rd Faculty of Medicine Charles University and Thomayer University Hospital 140 59 Prague Czech Republic

Department of Neurology 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady 100 34 Prague Czech Republic

Department of Pathology 1st Faculty of Medicine Charles University and General University Hospital 128 00 Prague Czech Republic

Department of Pathology 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady 100 34 Prague Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Charles University and Thomayer University Hospital 140 59 Prague Czech Republic

Department of Radiology Na Homolce Hospital 150 00 Prague Czech Republic

Faculty of Nuclear Sciences and Physical Engineering Czech Technical University 115 19 Prague Czech Republic

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