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Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt-Jakob disease: results from the Swedish Mortality Registry


Skillbäck, Tobias, Rosén, Christoffer, Asztely, Fredrik, Mattsson, Niklas, Blennow, Kaj, Zetterberg, Henrik


JAMA Neurology, Volume: 71, No.: 4, Pages.: 476-483

Year of Publication



Importance: Identifying a clinical distinction between the invariably lethal prion disease Creutzfeldt-Jakob disease (CJD) and nonprion rapidly progressive dementias is important and sometimes difficult; thus, reliable tools for diagnosis are in great demand.; Objective: To test the diagnostic performance of dementia cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and the T-tau to P-tau ratio for CJD by analyzing the results from a large database of routine clinical samples in combination with diagnosis information from the Swedish Mortality Registry.; Design, Setting, and Participants: This was a retrospective cohort study. We cross-referenced the Swedish Mortality Registry with a data set of CSF measurements of T-tau and P-tau performed in routine clinical testing at the Clinical Neurochemistry Laboratory of the Sahlgrenska University Hospital, which serves most of Sweden. The data set consisted of 9765 deceased individuals with CSF measures, including 93 with CJD, with 52 autopsy-verified samples (56%).; Main Outcomes and Measures: For each patient, T-tau and P-tau levels in CSF were measured and the T-tau to P-tau ratio was calculated. Biomarker levels (adjusted for age and sex) were analyzed in relation to the recorded cause of death and time of death. We specifically tested a previously defined CJD biomarker profile (T-tau >1400 ng/L and T-tau to P-tau-ratio >25).; Results: Patients who died of CJD had elevated CSF T-tau levels and T-tau to P-tau ratio, but not elevated CSF P-tau levels, compared with patients who died of Alzheimer disease (AD) and other dementias. The previously defined biomarker profile had a specificity of 99.0%, a sensitivity of 78.5%, and a positive likelihood ratio of 79.9. When tested against common differential diagnoses, the sensitivity, specificity, and positive likelihood ratio of this profile was 78.5%, 99.6%, and 196.6, respectively, in relation to AD and 78.5%, 99.3%, and 109.3, respectively, in relation to other dementias. In CJD individuals (n = 30) with repeated measurements, but not in those with AD (n = 242) or other dementias (n = 258), T-tau levels and T-tau to P-tau ratios increased over time.; Conclusions and Relevance: In this routine clinical setting, the combination of increased T-tau levels and increased T-tau to P-tau ratios in CJD patients has a very high specificity against important differential diagnoses to CJD and may serve as a clinically useful diagnostic test.;

Bibtex Citation

@article{Skillb_ck_2014, doi = {10.1001/jamaneurol.2013.6455}, url = {}, year = 2014, month = {apr}, publisher = {American Medical Association ({AMA})}, volume = {71}, number = {4}, pages = {476}, author = {Tobias Skillbäck and Christoffer Ros{'{e}}n and Fredrik Asztely and Niklas Mattsson and Kaj Blennow and Henrik Zetterberg}, title = {Diagnostic Performance of Cerebrospinal Fluid Total Tau and Phosphorylated Tau in Creutzfeldt-Jakob Disease}, journal = {{JAMA} Neurology} }


aged, aged, 80 and over, biological markers, cerebrospinal fluid, cjd, cohort studies, diagnosis, diagnosis, differential, epidemiology, female, genetics, humans, longitudinal studies, male, middle aged, mortality, phosphorylation, registries, retrospective studies, survival rate, sweden, tau proteins, trends

Countries of Study


Types of Dementia

Alzheimer’s Disease, Dementia (general / unspecified)

Types of Study

Cohort Study

Type of Outcomes


Type of Interventions

Diagnostic Target Identification

Diagnostic Targets

Biological Testing