Sporadic Creutzfeldt-Jakob Disease and Other Proteinopathies in Comorbidity

Frontiers in Neurology

Christine Van Broeckhoven¹  Julie van der Zee¹  Lubina Dillen¹  Robert Rusina²  Radoslav Matej⁵  Eva Parobkova⁶ 

[1] Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium;Department of Neurology, Third Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia;Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia;Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czechia;Department of Pathology, Third Faculty of Medicine, Charles University and Kralovske Vinohrady University Hospital, Prague, Czechia;National Reference Laboratory for Human Prion Diseases, Thomayer Hospital, Prague, Czechia;Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, Vlaams Instituut voor Biotechnologie (VIB), Antwerp, Belgium;

关键词: Creutzfeldt-Jakob disease;    Alzheimer's disease;    β amyloid;    tau protein;    neurodegenerative disease;   

DOI  :  10.3389/fneur.2020.596108

来源: DOAJ

【 摘 要 】

Background: Sporadic Creutzfeldt–Jakob disease (sCJD) is the most common type of a group of transmissible spongiform encephalopathies (prion diseases). The etiology of the sporadic form of CJD is still unclear. sCJD can occur in combination with other neurodegenerative diseases, which further complicates the diagnosis. Alzheimer's disease (AD), e.g., is often seen in conjunction with sCJD.Method: In this study, we performed a systematic analysis of 15 genes related to the most important neurodegenerative diseases - AD, frontotemporal dementia, amyotrophic lateral sclerosis, prion disease, and Parkinson's disease - in a cohort of sCJD and sCJD in comorbidity with AD and primary age-related proteinopathy (PART). A total of 30 neuropathologically verified cases of sCJD with and without additional proteinopathies were included in the study. In addition, we compared microtubule-associated protein tau (MAPT) haplotypes between sCJD patients and patients with sCJD and PART or sCJD and AD. Then we studied the interaction between the Apolipoprotein E gene (APOE) and PRNP in sCJD patients.Results: We did not find any causal mutations in the neurodegenerative disease genes. We did detect a p.E318G missense variant of uncertain significance (VUS) in PSEN1 in three patients. In PRNP, we also found a previously described non-pathogenic insertion (p.P84_Q91Q).Conclusion: Our pilot study failed to find any critical differences between pure sCJD and sCJD in conjunction with other comorbid neurodegenerative diseases. Further investigations are needed to better understand this phenomenon.

【 授权许可】

Unknown