Contribution of Cerebrospinal Fluid Thymosin β4 Levels to the Clinical Differentiation of Creutzfeldt-Jakob Disease

Objective: To asses thymosin beta 4 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 beta 4 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 beta 4 test results in CJD and other dementia. Results: The thymosin beta 4 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 beta 4 relative peak area, we estimated 100% sensitivity with 98.5% specificity. Conclusion: These findings indicate that cerebrospinal fluid levels of thymosin beta 4 protein measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry may effectively contribute to discriminate CJD from other forms of dementia.