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Original Contribution |

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

Maria Le Pera, PhD; Elena Urso, PhD; Teresa Sprovieri, PhD; Sabrina Bossio, PhD; Umberto Aguglia, MD; Ida Manna, PhD; Chiara Cupidi, MD; Tiziana Ferraro, PhD; Antonio Gambardella, MD; Antonio Qualtieri, PhD; Aldo Quattrone, MD
Arch Neurol. 2012;69(7):868-872. doi:10.1001/archneurol.2011.3558.
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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.

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Figures

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Figure 1. Comparison of thymosin β4 relative peak area (percentage of area) in the examined groups. A, Mean (SD) data statistically analyzed by t test. B, Individual values for each group. The line represents the optimal cutoff (1.2% area). AD indicates Alzheimer disease; CJD, Creutzfeldt-Jakob disease; FTD, frontotemporal dementia; NCIC, non–cognitively impaired control; and RPD, rapid-onset progressive dementia.

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Grahic Jump Location

Figure 2. Receiver operating characteristic analysis at different cutoff points of cerebrospinal fluid thymosin β4 levels. A, Receiver operating characteristic analysis for diagnosis of patients with Creutzfeldt-Jakob disease (n = 21) vs all other patients (n = 67).The area under the curve was 0.998. B, Diagram for patients with Creutzfeldt-Jakob disease vs patients with dementia (n = 42). For this curve, the area under the curve was 0.998.

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