Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias
Abstract
Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker. Due to neuronal lysis the cytosolic fraction of total tau containing phosphorylated and non-phosphorylated isoforms is partially liberated into the CSF. Since hyperphosphorylation of tau may specifically occur in neurodegenerative diseases associated with neurofibrillary changes, we hypothesized that the phospho-tau (P-tau)/total tau ratio in CSF may be a useful marker to discriminate CJD from other neurodegenerative disorders. The P-tau/total tau ratio discriminated patients with CJD from all other neuro-degenerative disorders including patients with AD and FTD without any overlap. Although the results have to be confirmed in a larger sample, the preliminary data suggest that simultaneous measurement of total tau and P-tau in CSF may be useful to identify patients with CJD.
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These biomarkers (t-tau and p-tau) remain at normal concentrations in other neurodegenerative disorders with substantial neurodegeneration, and also those with tau pathology.
“However, these biomarkers remain at normal concentrations in other neurodegenerative disorders with substantial neurodegeneration,8, 9, 10 and also those with tau pathology.11, 12, 13”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [8]
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- Authors
- Riemenschneider, M., Wagenpfeil, S., Vanderstichele, H., Otto, M., Wiltfang, J., Kretzschmar, H., Vanmechelen, E., Förstl, H., & Kurz, A.
- Affiliations
- Technical University of Munich (DE)
- Fujirebio (Belgium) (BE)
- University of Göttingen (DE)
- Institut für Neuropathologie (DE)
- Corresponding author
- Riemenschneider, M
- Venue
- Molecular Psychiatry
- Published
- 2003-03
- Volume
- 8
- Issue
- 3
- Pages
- 343-347
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2087097612
- Cited by
- 238
- References
- 1
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 14 · 2021: 17 · 2020: 12 · 2019: 6 · 2018: 10 · 2017: 11 · 2016: 12 · 2015: 18 · 2014: 8 · 2013: 8 · 2012: 8
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- GRO (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Creutzfeldt-Jakob disease, cerebrospinal fluid biomarkers, tau hyperphosphorylation, Alzheimer's disease, frontotemporal lobar degeneration, differential diagnosis of dementia, neurodegenerative diseases, 14-3-3 proteins
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Diagnosis, Differential, Female, Humans, Creutzfeldt-Jakob Syndrome, Male, Middle Aged, Phosphoproteins, Phosphorylation, tau Proteins
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