The role of cerebrospinal fluid proteins as early diagnostic markers for sporadic Creutzfeldt-Jakob disease

Abstract

The utility of cerebrospinal fluid (CSF) proteins such as 14-3-3, tau protein and S-100b as diagnostic markers in the early stages of sporadic Creutzfeldt-Jakob disease (sCJD) is unclear. We examined the diagnostic value of these CSF proteins in the early stages of sCJD (within 6 weeks of onset of symptoms). Four groups of patients were compared: patients with probable or neuropathologically confirmed sCJD with CSF taken within 6 weeks of onset ('sCJD<6-week group', n=47); patients with CSF taken within 6 weeks of disease onset but with a diagnosis other than CJD ('non-sCJD<6-week group', n=21); patients with neuropathologically proven sCJD where CSF was taken later than 6 weeks after onset ('sCJD>6-week group', n=206); patients with CSF taken later than 6 weeks after onset of symptoms but with a diagnosis other than CJD ('non-sCJD>6-week group', n=166). The sensitivity and specificity of different combinations of neuronal proteins were ascertained. The sensitivities of all three markers were similar and ranged from 96% to 98%. The sensitivity of these markers was greater in the 'sCJD<6-week group' than in the 'sCJD>6-week group'. This may be due to differences in the PRNP codon 129 and PrP isotype distribution between these groups. CSF tau protein had the greatest specificity (82%). We found all three CSF protein markers to be highly sensitive in the early stages of sCJD, with CSF tau protein having the greatest specificity and efficiency. Our findings indicate that CSF protein markers are effective tests in the early stages of sCJD.