thymosin and Creutzfeldt-Jakob-Syndrome

To asses thymosin β4 specificity as relevant to the diagnosis of Creutzfeldt-Jakob disease (CJD).. 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.. National Research Council, Cosenza, Italy.. 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.. The thymosin β4 test results in CJD and other dementia.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Creutzfeldt-Jakob Syndrome; Disease Progression; Frontotemporal Dementia; Humans; Middle Aged; ROC Curve; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Statistics, Nonparametric; Thymosin

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been applied to the analysis of a wide range of biomolecules. To date, there are two specific areas of application where MALDI-TOF-MS is viewed as impractical: analysis of low-mass analytes and relative quantitative applications. However, these limitations can be overcome and quantification can be routine. Increased levels of thymosin beta(4) (TB4) have been recently found in cerebrospinal fluid (CSF) from Creutzfeldt-Jakob disease (CJD) patients. Our objective was to apply a label-free quantitative application of MALDI-TOF-MS to measure TB4 levels in human CSF by adding the oxidized form of TB4 as an internal standard. The relative peak area or peak height ratios of the native TB4 to the added oxidized form were evaluated. Considering the relative peak area ratios, healthy individuals showed a mean value of 40.8+/-21.27 ng/ml, whereas CJD patients showed high values with a mean of 154+/-59.07 ng/ml, in agreement with the previous observation found in CJD patients. Similar results were obtained considering peak height ratios. The proposed method may provide a simple and rapid screening method for quantification on CSF of TB4 levels suitable for diagnostic purposes.

Topics: Amino Acid Sequence; Creutzfeldt-Jakob Syndrome; Humans; Molecular Sequence Data; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thymosin