Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients.
The clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and beta amyloid (Abeta42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Abeta42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b-93/93%, t-tau-93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Abeta42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.
Neurology Department, Laboratory of Neurochemistry, Coimbra University Hospital, Praceta Mota Pinto, 3000 Coimbra, Portugal. ines.baldeiras@sapo.pt
Inês Esteves
IE
Baldeiras
Maria Helena
MH
Ribeiro
Paula
P
Pacheco
Alvaro
A
Machado
Isabel
I
Santana
Luís
L
Cunha
Catarina Resende
CR
Oliveira
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011174:Portugal; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid*; D012680:Sensitivity and Specificity; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D048948:14-3-3 Proteins; D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; D009414:Nerve Growth Factors; C512656:PRNP protein, human; D010446:Peptide Fragments; D000072002:Prion Proteins; D011328:Prions; D020033:Protein Isoforms; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins