RESEARCH HIGHLIGHTS Nature Reviews Neurology 10, 180 (2014); published online 11 March 2014; doi:10.1038/nrneurol.2014.39
PRION DISEASE
Cerebrospinal fluid tau levels—a potential diagnostic biomarker for Creutzfeldt–Jakob disease Levels of tau protein in the cerebrospinal fluid (CSF) could aid the differential diagnosis of Creutzfeldt–Jakob disease (CJD), according to a report in JAMA Neurology. Drawing on data from the Swedish Mortality Registry, Tobias Skillbäck and colleagues found that a combination of elevated total tau (T-tau) levels and an increased ratio of T-tau to phosphorylated tau (P-tau) could reliably distinguish patients with CJD from those with Alzheimer disease (AD) or other non-prion dementias.
‘‘
…we saw our chance to study the diagnostic value of these CSF measurements
’’
“We cross-referenced the available CSF analyses stored in the laboratory database at the Sahlgrenska University Hospital with the Swedish Mortality Registry and found that a substantial number
of people with CJD were represented in the material,” explains Skillbäck. “Since CJD is notoriously hard to clinically diagnose, we saw our chance to study the diagnostic value of these CSF measurements.” From a cohort of 9,765 individuals recorded in the Swedish Mortality Registry, Skillbäck et al. identified 93 patients in whom CJD was cited as a cause of death. The diagnosis was verified by autopsy in 52 cases. In this cohort, a predefined CSF biomarker profile—T-tau >1,400 ng/l and T-tau:P-tau ratio >50— had a specificity of 99.0% and a sensitivity of 78.5% for the differentiation of CJD from non-prion dementias. For 30 of the patients with CJD, more than one tau measurement was available, thereby enabling Skillbäck and his colleagues to perform a longitudinal analysis. T-tau levels and T-tau:P-tau ratios were found to increase in parallel with disease progression in CJD, reaching
NATURE REVIEWS | NEUROLOGY
a peak just before death. By contrast, in patients with AD or other non-prion dementias, levels of these biomarkers remained stable in the period leading up to death. “Previous studies have shown that tau levels in CSF are high in patients with CJD, but the distinction against other dementias has not been thoroughly investigated,” says Skillbäck. “The next step is to establish the positive and negative predictive values of the tau markers in patients with clinical symptoms that lead the physician to consider CJD— the most relevant clinical context that one could imagine.” Heather Wood Original article Skillbäck, T. et al. Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt–Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol. doi:10.1001/ jamaneurol.2013.6455
VOLUME 10 | APRIL 2014 © 2014 Macmillan Publishers Limited. All rights reserved
PRION DISEASE
Cerebrospinal fluid tau levels—a potential diagnostic biomarker for Creutzfeldt–Jakob disease Levels of tau protein in the cerebrospinal fluid (CSF) could aid the differential diagnosis of Creutzfeldt–Jakob disease (CJD), according to a report in JAMA Neurology. Drawing on data from the Swedish Mortality Registry, Tobias Skillbäck and colleagues found that a combination of elevated total tau (T-tau) levels and an increased ratio of T-tau to phosphorylated tau (P-tau) could reliably distinguish patients with CJD from those with Alzheimer disease (AD) or other non-prion dementias.
‘‘
…we saw our chance to study the diagnostic value of these CSF measurements
’’
“We cross-referenced the available CSF analyses stored in the laboratory database at the Sahlgrenska University Hospital with the Swedish Mortality Registry and found that a substantial number
of people with CJD were represented in the material,” explains Skillbäck. “Since CJD is notoriously hard to clinically diagnose, we saw our chance to study the diagnostic value of these CSF measurements.” From a cohort of 9,765 individuals recorded in the Swedish Mortality Registry, Skillbäck et al. identified 93 patients in whom CJD was cited as a cause of death. The diagnosis was verified by autopsy in 52 cases. In this cohort, a predefined CSF biomarker profile—T-tau >1,400 ng/l and T-tau:P-tau ratio >50— had a specificity of 99.0% and a sensitivity of 78.5% for the differentiation of CJD from non-prion dementias. For 30 of the patients with CJD, more than one tau measurement was available, thereby enabling Skillbäck and his colleagues to perform a longitudinal analysis. T-tau levels and T-tau:P-tau ratios were found to increase in parallel with disease progression in CJD, reaching
NATURE REVIEWS | NEUROLOGY
a peak just before death. By contrast, in patients with AD or other non-prion dementias, levels of these biomarkers remained stable in the period leading up to death. “Previous studies have shown that tau levels in CSF are high in patients with CJD, but the distinction against other dementias has not been thoroughly investigated,” says Skillbäck. “The next step is to establish the positive and negative predictive values of the tau markers in patients with clinical symptoms that lead the physician to consider CJD— the most relevant clinical context that one could imagine.” Heather Wood Original article Skillbäck, T. et al. Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt–Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol. doi:10.1001/ jamaneurol.2013.6455
VOLUME 10 | APRIL 2014 © 2014 Macmillan Publishers Limited. All rights reserved
