ERK2 is increased in cerebrospinal fluid of Creutzfeldt-Jakob disease patients.
The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by several biochemical markers in cerebrospinal fluid (CSF) such as 14-3-3 proteins and tau protein. Unfortunately, none of the currently known markers are suited for screening or seems to be directly related to the pathophysiological process. A marker fulfilling these criteria might facilitate the early detection and might also serve in monitoring drug efficacy. Recently, the extracellular signal-regulated kinase ERK1/2 was detected in CSF of patients with neuropsychiatric disorders. Furthermore, ERK1/2 was reported to be activated in brains of animals infected with pathological prion protein. Therefore, we investigated CSF of 19 patients with CJD, 23 patients with other dementias including patients with Alzheimer's disease, and 12 patients with other neurological disorders. The measurement of ERK1/2 in the CSF samples was performed with an electrochemiluminescence assay and Western immunoblot. ERK1/2 and doubly phosphorylated ERK1/2 (pERK1/2) were detected in all patient groups. Significantly elevated mean levels of total ERK1/2 and pERK1/2 were found in the CJD patients. This increase was also observed in a CJD case that was negative for 14-3-3 protein or in CJD cases that had low levels of tau protein. Western immunoblot analysis suggested that ERK2 was the predominant form of ERKs present in our CSF samples. This pilot study suggests that ERK1/2 is a potential CSF biomarker for CJD, directly associated with the pathophysiological processes. Analysis of larger sample cohorts including other diseases with rapid neurodegeneration are required to confirm our findings.
Steinacker
Petra
P
Department of Neurology, University of Ulm, Ulm, Germany.
Klafki
Hans
H
Lehnert
Stefan
S
Jesse
Sarah
S
Arnim
Christine A F V
CA
Tumani
Hayrettin
H
Pabst
Alice
A
Kretzschmar
Hans A
HA
Wiltfang
Jens
J
Otto
Markus
M
D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis / Q000134:cerebrospinal fluid*; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D010865:Pilot Projects
D015415:Biomarkers; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3