An atypical case of Creutzfeldt-Jakob disease mimicking frontotemporal dementia: genotypic influence and clinical implications

We report an atypical case of Creutzfeldt-Jakob Disease (CJD) mimicking Frontotemporal Dementia (FTD) in a 68-year-old male. The patient initially presented with an anxious-depressive syndrome, progressing over 29 months to include dysexecutive syndrome, stereotyped speech, inertia, social withdrawal, verbal fluency impairments, and marked dyspraxia. Diagnostic imaging revealed signal alterations on MRI, while CSF analysis showed elevated T-TAU, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels. A second-generation RT-QuIC (SG-RT-QuIC) confirmed prion disease, with genetic testing identifying a codon 129 MV polymorphism and a deletion in the third octapeptide repeat. This case highlights the importance of integrating advanced diagnostic tools, such as SG-RT-QuIC and comprehensive genotyping, in evaluating atypical presentations of CJD. Early elevated GFAP levels highlight the usefulness of considering neuroinflammatory markers in slowly progressive forms of CJD.