CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
PLoS One. 2012;7(3):e32664. doi: 10.1371/journal.pone.0032664. Epub 2012 Mar 2.
The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are important second messengers and are potential biomarkers for Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Creutzfeldt-Jakob disease (CJD).
METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS) the cerebrospinal fluid (CSF) concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15) had lower cAMP (-70%) and cGMP (-55%) concentrations in CSF compared with controls (n = 11). There was no difference in PD, PD dementia (PDD) and ALS cases. Receiver operating characteristic (ROC) curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC) of 0.86 (cAMP) and 0.85 (cGMP). We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92) and to 93% and 100% for the ratio tau/cAMP (AUC 0.99).
CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.
环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）是重要的第二信使，是帕金森病（PD）、肌萎缩侧索硬化症（ALS）和克雅氏病（CJD）的潜在生物标志物。
方法/主要发现：在这里，我们通过液相色谱/串联质谱法（LC-MS/MS）检测了 82 例患者的脑脊液（CSF）中 cAMP 和 cGMP 的浓度，并评估了它们作为生物标志物的诊断效力。为了与公认的生物标志物进行比较，我们测量了 CJD 和对照患者 CSF 中的tau 浓度。与对照组（n=11）相比，CJD 患者（n=15）的 CSF 中 cAMP（-70%）和 cGMP（-55%）浓度较低。PD、PD 痴呆（PDD）和 ALS 病例之间无差异。受试者工作特征（ROC）曲线分析证实 cAMP 和 cGMP 是 CJD 的有价值的诊断标志物，曲线下面积（AUC）分别为 0.86（cAMP）和 0.85（cGMP）。我们计算出 cAMP 的敏感性为 100%，特异性为 64%，cGMP 的敏感性为 67%，特异性为 100%。这两种核苷酸的组合使 cAMPxcGMP（AUC 0.92）的敏感性提高到 80%，特异性提高到 91%，tau/cAMP（AUC 0.99）的比值提高到 93%和 100%。
结论/意义：我们得出结论，CSF 中 cAMP 和 cGMP 的测定可轻易纳入 CJD 的诊断中，并有助于监测疾病进展和治疗控制。
