Measurement of ERK 1/2 in CSF from Patients with Neuropsychiatric Disorders and Evidence for the Presence of the Activated Form

Article type: Research Article

Authors: Klafki, Hans-Wolfgang^{a; j; *} | Lewczuk, Piotr^a | Kamrowski-Kruck, Heike^{a; j} | Maler, Juan Manuel^a | Müller, Katharina^a | Peters, Oliver^b | Heuser, Isabella^b | Jessen, Frank^c | Popp, Julius^c | Frölich, Lutz^d | Wolf, Stefanie^e | Prinz, Berit^e | Luckhaus, Christian^f | Schröder, Johannes^g | Pantel, Johannes^h | Gertz, Hermann-Josefⁱ | Kölsch, Heike^c | Müller, Bernhard W.^j | Esselmann, Hermann^{a; j} | Bibl, Mirko^{e; j} | Kornhuber, Johannes^a | Wiltfang, Jens^{a; j}

Affiliations: [a] Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany | [b] Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Berlin, Germany | [c] Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany | [d] Division of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany | [e] Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany | [f] Department of Psychiatry and Psychotherapy, University of Düsseldorf, Düsseldorf, Germany | [g] Section of Geriatric Psychiatry, University of Heidelberg, Heidelberg, Germany | [h] Department of Psychiatry, Psychosomatic and Psychotherapy, University of Frankfurt, Germany | [i] Department of Psychiatry, University of Leipzig, Leipzig, Germany | [j] Present address: Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, LVR-Klinikum Essen, Essen, Germany

Correspondence: [*] Corresponding author: Hans-Wolfgang Klafki, Department of Psychiatry and Psychotherapy, Laboratory for Molecular Neurobiology, University of Duisburg-Essen, LVR-Klinikum Essen, Virchowstr. 171, D-45147 Essen, Germany. Tel.: +49 201 723 4225; Fax: +49 201 723 5543; E-mail: hans.klafki@uni-due.de.

Abstract: The clinical diagnosis of neurodegenerative disorders can be supported by soluble biomarkers in cerebrospinal fluid (CSF), such as tau protein, phospho-tau, and amyloid-β peptides. In particular, increased CSF levels of phospho-tau in Alzheimer's disease appear to reflect disease specific pathological processes. We report here evidence for the presence of soluble MAP-kinase ERK1/2 in a small set of human CSF samples from patients with Alzheimer's disease, frontotemporal degeneration, and mild cognitive impairment. The level of total ERK1/2 in CSF as measured by electrochemiluminescent assay was correlated with that of total tau and phospho-tau. A small fraction of ERK1/2 in a pooled CSF sample was found to be in the doubly phosphorylated (activated) state. Our findings suggest that i) MAP kinase ERK1/2 is apparently released under neurodegenerative conditions in parallel with tau and phospho-tau and ii) in the future, it might be possible to find in CSF samples evidence for disease related alterations in brain kinase signaling pathways by use of highly sensitive and activation-state specific anti-kinase antibodies.

Keywords: Alzheimer's disease, cerebrospinal fluid, ERK1/2, frontotemporal degeneration, MAP kinase, mild cognitive impairment, tau

DOI: 10.3233/JAD-2009-1167

Journal: Journal of Alzheimer's Disease, vol. 18, no. 3, pp. 613-622, 2009