Cerebrospinal fluid markers in sporadic Creutzfeldt-Jakob disease.
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated(181) tau, and amyloid beta (Aβ) peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most sensitive indicators of sCJD, the highest sensitivity, specificity and positive predictive value were obtained when all the above markers were combined. The latter approach also allowed a reliable differential diagnosis with other neurodegenerative dementias.
Section of Neuropathology, Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; E-Mails:  michele.fiorini@univr.it  (M.F.);  sergio.ferrari@ospedaleuniverona.it  (S.F.).
Gianluigi
G
Zanusso
Michele
M
Fiorini
Sergio
S
Ferrari
Alberto
A
Gajofatto
Annachiara
A
Cagnin
Andrea
A
Galassi
Silvia
S
Richelli
Salvatore
S
Monaco
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D000075202:Contraindications; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D011237:Predictive Value of Tests; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
D048948:14-3-3 Proteins; D016229:Amyloid beta-Peptides; D015415:Biomarkers; C512656:PRNP protein, human; D010446:Peptide Fragments; D000072002:Prion Proteins; D011328:Prions; C075222:amyloid beta-protein (1-42); D016875:tau Proteins