Contribution of cerebrospinal fluid thymosin β4 levels to the clinical differentiation of Creutzfeldt-Jakob disease

Objective To asses thymosin β4 specificity as relevant to the diagnosis of Creutzfeldt-Jakob disease (CJD). Design A matrix-assisted laser desorption ionization time-of-flight mass spectrometry protein profiling analysis was applied to several neurological disorders that are known to lead to dementia. The relative peak area (percentage of area) of the thymosin β4 MS signal was taken into account. Setting National Research Council, Cosenza, Italy. Patients Cerebrospinal fluid analysis was performed on 21 patients with neuropathologically confirmed CJD; 15 patients with frontotemporal dementia; 18 patients with probable Alzheimer disease; and 9 patients with a rapid-onset progressive dementia. A non–cognitively impaired control group consisted of 25 individuals without CJD or dementia. Main Outcome Measures The thymosin β4 test results in CJD and other dementia. Results The thymosin β4 cerebrospinal fluid levels appeared to be markedly increased in CJD samples compared with frontotemporal cases (P = 10−7) and patients with Alzheimer disease (P = 10−7). A lower significance was observed vs the group with rapid-onset progressive dementia (P = .0004). Thus, at a cutoff value of 1.2% of the thymosin β4 relative peak area, we estimated 100% sensitivity with 98.5% specificity. Conclusion These findings indicate that cerebrospinal fluid levels of thymosin β4 protein measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry may effectively contribute to discriminate CJD from other forms of dementia.