Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.
The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p < 0.001), MV (p = 0.004), and VV (p = 0.001) genotype. Receiver operating characteristic analyses showed values of area under the curve of 0.76-0.80 for the different genotypes indicating a good diagnostic validity of the test. Total tau can be used as a diagnostic test for the assessment of prion protein type when codon 129 genotype is known. It provides valuable information for physicians and next of kin about the further course of disease.
Epidemiological and Statistical Methods (ESME), Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany; National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany; German Center for Infection Research (DZIF), Hannover, Germany. Electronic address: andre.karch@helmholtz-hzi.de.
André
A
Karch
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany.
Peter
P
Hermann
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany.
Claudia
C
Ponto
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Matthias
M
Schmitz
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany.
Amandeep
A
Arora
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany.
Saima
S
Zafar
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Franc
F
Llorens
Institute of Biostatistics, Hannover Medical School (MHH), Hannover, Germany.
Annika
A
Müller-Heine
National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Inga
I
Zerr
D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011328:Prions / Q000145:classification / Q000235:genetics; D011379:Prognosis; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D003062:Codon; D011328:Prions; D016875:tau Proteins
Biomarker; Creutzfeldt-Jakob disease; Neurodegeneration; Subtype; Tau