title: CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob disease but not Parkinson's disease and amyotrophic lateral sclerosis.
abstract: BACKGROUND
  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).
  
  
  RESULTS
  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
  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.
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Oeckl
authors.forename: Petra
authors.initials: P
authors.lastname: Steinacker
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehnert
authors.forename: Sarah
authors.initials: S
authors.lastname: Jesse
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
authors.forename: Boris
authors.initials: B
authors.lastname: Ferger
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid*; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid*; D006152:Cyclic GMP / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D016875:tau Proteins / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D016875:tau Proteins; D000242:Cyclic AMP; D006152:Cyclic GMP