Abstract
BackgroundThe 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 FindingsHere, 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/SignificanceWe 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.
Highlights
The cyclic nucleotides cyclic adenosine-39,59-monophosphate and cyclic guanosine-39,59-monophosphate are important second messengers
The aim of the present study is to investigate cAMP and cGMP in cerebrospinal fluid (CSF) of Parkinson’s disease (PD), PD dementia (PDD), amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD) and control patients
Whether cAMP and cGMP concentrations correlated with the survival of the CJD patients
Summary
The cyclic nucleotides cyclic adenosine-39,59-monophosphate (cAMP) and cyclic guanosine-39,59-monophosphate (cGMP) are important second messengers. Examples are signal transduction in synapses, communication between neurons and glia cells or inflammatory processes [2,3]. Alterations of these second messengers affect normal brain function and can be found in several neurological diseases. In Creutzfeldt-Jakob disease (CJD) a reduced expression of soluble guanylate cyclase b1 in astrocytes in the white matter [8] has been shown but data on cGMP concentrations from human brain samples in CJD are missing. The cyclic nucleotides cyclic adenosine-39,59-monophosphate (cAMP) and cyclic guanosine-39,59-monophosphate (cGMP) are important second messengers and are potential biomarkers for Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Creutzfeldt-Jakob disease (CJD)
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