Human prion disorders (transmissible spongiform encephalopathies, TSEs) are unique, progressive, and fatal neurodegenerative diseases caused by aggregation of misfolded prion protein in neuronal tissue. Due to the potential transmission, human TSEs are under active surveillance in a majority of countries; in the Czech Republic data are centralized at the National surveillance center (NRL) which has a clinical and a neuropathological subdivision. The aim of our article is to review current knowledge about human TSEs and summarize the experience of active surveillance of human prion diseases in the Czech Republic during the last 20 years. Possible or probable TSEs undergo a mandatory autopsy using a standardized protocol. From 2001 to 2020, 305 cases of sporadic and genetic TSEs including 8 rare cases of Gerstmann-Sträussler-Scheinker syndrome (GSS) were confirmed. Additionally, in the Czech Republic, brain samples from all corneal donors have been tested by the NRL immunology laboratory to increase the safety of corneal transplants since January 2007. All tested 6590 corneal donor brain tissue samples were negative for prion protein deposits. Moreover, the routine use of diagnostic criteria including biomarkers are robust enough, and not even the COVID-19 pandemic has negatively impacted TSEs surveillance in the Czech Republic.

• Keywords
• Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker syndrome, corneal donor, prion protein, transmissible spongiform encephalopathies,
• Publication type
• Journal Article MeSH
• Review MeSH

Various proteins play a decisive role in the pathology of different neurodegenerative diseases. Nonetheless, most of these proteins can only be detected during a neuropathological assessment, although some non-specific biomarkers are routinely tested for in the cerebrospinal fluid (CSF) as a part of the differential diagnosis of dementia. In antemortem CSF samples from 117 patients with different types of neuropathologically confirmed neurodegenerative disease with dementia, we assessed total-tau (t-tau), phosphorylated-tau (181P) (p-tau), amyloid-beta (1-42) (Aβ42), TAR DNA binding protein (TDP)-43, progranulin (PGRN), and neurofilament light (NfL) chain levels, and positivity of protein 14-3-3. We found t-tau levels and the t-tau/p-tau ratios were significantly higher in prion diseases compared to the other neurodegenerative diseases. Statistically significant differences in the t-tau/Aβ42 ratio predominantly corresponded to t-tau levels in prion diseases and Aβ42 levels in AD. TDP-43 levels were significantly lower in prion diseases. Additionally, the TDP-43/Aβ42 ratio was better able to distinguish Alzheimer's disease from other neurodegenerative diseases compared to using Aβ42 alone. In frontotemporal lobar degeneration, PRGN levels were significantly higher in comparison to other neurodegenerative diseases. There is an increasing need for biomarkers suitable for diagnostic workups for neurodegenerative diseases. It appears that adding TDP-43 and PGRN to the testing panel for neurodegenerative diseases could improve the resolution of differential diagnoses.

• MeSH
• Amyloid beta-Peptides cerebrospinal fluid   MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Dementia cerebrospinal fluid   classification   diagnosis   MeSH
• Diagnosis, Differential MeSH
• DNA-Binding Proteins cerebrospinal fluid   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neurofilament Proteins cerebrospinal fluid   MeSH
• Peptide Fragments cerebrospinal fluid   MeSH
• Autopsy MeSH
• Progranulins cerebrospinal fluid   MeSH
• 14-3-3 Proteins cerebrospinal fluid   MeSH
• tau Proteins cerebrospinal fluid   MeSH
• Cerebrospinal Fluid Proteins cerebrospinal fluid   MeSH
• Gene Expression Regulation MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• amyloid beta-protein (1-42) MeSH Browser
• Amyloid beta-Peptides MeSH
• Biomarkers MeSH
• DNA-Binding Proteins MeSH
• GRN protein, human MeSH Browser
• MAPT protein, human MeSH Browser
• neurofilament protein L MeSH Browser
• Neurofilament Proteins MeSH
• Peptide Fragments MeSH
• Progranulins MeSH
• 14-3-3 Proteins MeSH
• tau Proteins MeSH
• Cerebrospinal Fluid Proteins MeSH
• TARDBP protein, human MeSH Browser