Association of Blood and Cerebrospinal Fluid Tau Level and Other Biomarkers With Survival Time in Sporadic Creutzfeldt-Jakob Disease
Open accessAbstract
IMPORTANCE: Fluid biomarkers that can predict survival time in sporadic Creutzfeldt-Jakob disease (sCJD) will be critical for clinical care and for treatment trials. OBJECTIVE: To assess whether plasma and cerebrospinal fluid (CSF) biomarkers are associated with survival time in patients with sCJD. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal cohort study, data from 193 patients with probable or definite sCJD who had codon 129 genotyping referred to a tertiary national referral service in the United States were collected from March 2004 to January 2018. Participants were evaluated until death or censored at the time of statistical analysis (range, 0.03-38.3 months). We fitted Cox proportional hazard models with time to event as the outcome. Fluid biomarkers were log-transformed, and models were run with and without nonfluid biomarkers of survival. Five patients were excluded because life-extending measures were performed. MAIN OUTCOMES AND MEASURES: Biomarkers of survival included sex, age, codon 129 genotype, Barthel Index, Medical Research Council Prion Disease Rating Scale, 8 CSF biomarkers (total tau [t-tau] level, phosphorylated tau [p-tau] level, t-tau:p-tau ratio, neurofilament light [NfL] level, β-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test), and 3 plasma biomarkers (t-tau level, NfL level, and glial fibrillary acidic protein level). RESULTS: Of the 188 included participants, 103 (54.8%) were male, and the mean (SD) age was 63.8 (9.2) years. Plasma t-tau levels (hazard ratio, 5.8; 95% CI, 2.3-14.8; P < .001) and CSF t-tau levels (hazard ratio, 1.6; 95% CI, 1.2-2.1; P < .001) were significantly associated with survival after controlling for codon 129 genotype and Barthel Index, which are also associated with survival time. Plasma and CSF t-tau levels were correlated (r = 0.74; 95% CI, 0.50-0.90; P < .001). Other fluid biomarkers associated with survival included plasma NfL levels, CSF NfL levels, t-tau:p-tau ratio, 14-3-3 test result, and neuron-specific enolase levels. In a restricted subset of 23 patients with data for all significant biomarkers, the hazard ratio for plasma t-tau level was more than 40% larger than any other biomarkers (hazard ratio, 3.4; 95% CI, 1.8-6.4). CONCLUSIONS AND RELEVANCE: Cerebrospinal fluid and plasma tau levels, along with several other fluid biomarkers, were significantly associated with survival time in patients with sCJD. The correlation between CSF and plasma t-tau levels and the association of plasma t-tau level with survival time suggest that plasma t-tau level may be a minimally invasive fluid biomarker in sCJD that could improve clinical trial stratification and guide clinical care.
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In Creutzfeldt-Jakob disease, plasma and CSF total tau correlate strongly, and both the concentration range and species diversity in these fluids exceed those in Alzheimer disease or frontotemporal lobar degeneration.
“This contrasts with a strong correlation of plasma and CSF t-tau concentration in Creutzfeldt-Jakob disease, in which the range of t-tau concentrations and species in plasma and CSF is higher than in AD or FTLD.40”
From Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease (2021) · cites this paper as [40]
The Baseline Characteristics section reports a strong correlation between plasma and CSF total tau in sporadic CJD (r = 0.74). The Discussion mentions greater serum tau elevations in CJD than in other neurodegenerative conditions, but it does not establish that concentration ranges in both fluids exceed those in AD or FTLD. Our copy does not compare tau species diversity across these diseases. Page numbers were not available in the indexed passages. (LLM, conf=0.88)
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Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease
Illán-Gala, I., Lleo, A., Karydas, A., Staffaroni, A. M., Zetterberg, H., Sivasankaran, R., Grinberg, L. T., Spina, S., Kramer, J. H., Ramos, E. M., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000011226 · Cited by 150 · see citing works
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- Authors
- Staffaroni, A. M., Kramer, A. O., Casey, M., Kang, H., Rojas, J. C., Orrú, C. D., Caughey, B., Allen, I. E., Kramer, J. H., Rosen, H. J., Blennow, K., Zetterberg, H., & Geschwind, M. D.
- Affiliations
- University of California, San Francisco (US)
- Palo Alto University (US)
- Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana
- National Institutes of Health (US)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Staffaroni, Adam M.
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2019-08-01
- Volume
- 76
- Issue
- 8
- Pages
- 969
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC6503575
- OpenAlex
- W2943273256
- Cited by
- 100
- References
- 46
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 16 · 2023: 15 · 2022: 12 · 2021: 19 · 2020: 23 · 2019: 4
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute on Aging (K23AG059888, R56AG055619, K23AG021989, R01AG031189, K24AG045333, P01AG019724, T32AG023481)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- sporadic Creutzfeldt-Jakob disease, survival time, total tau, phosphorylated tau, neurofilament light chain, cerebrospinal fluid biomarkers, plasma biomarkers, prion disease, prognostic factors, amyloid-beta 42
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