Measurement of ERK 1/2 in CSF from patients with neuropsychiatric disorders and evidence for the presence of the activated form.
The clinical diagnosis of neurodegenerative disorders can be supported by soluble biomarkers in cerebrospinal fluid (CSF), such as tau protein, phospho-tau, and amyloid-beta 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.
Klafki
Hans-Wolfgang
HW
Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany. hans.klafki@uni-due.de
Lewczuk
Piotr
P
Kamrowski-Kruck
Heike
H
Maler
Juan Manuel
JM
Müller
Katharina
K
Peters
Oliver
O
Heuser
Isabella
I
Jessen
Frank
F
Popp
Julius
J
Frölich
Lutz
L
Wolf
Stefanie
S
Prinz
Berit
B
Luckhaus
Christian
C
Schröder
Johannes
J
Pantel
Johannes
J
Gertz
Hermann-Josef
HJ
Kölsch
Heike
H
Müller
Bernhard W
BW
Esselmann
Hermann
H
Bibl
Mirko
M
Kornhuber
Johannes
J
Wiltfang
Jens
J
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D048049:Extracellular Signal-Regulated MAP Kinases / Q000134:cerebrospinal fluid / Q000235:genetics; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000134:cerebrospinal fluid* / Q000235:genetics*; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000235:genetics
D000911:Antibodies, Monoclonal; D016875:tau Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3