TDP-43 in cerebrospinal fluid of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
BACKGROUND
Recently, TAR DNA-binding protein 43 (TDP-43) was identified as the major component of ubiquitin-positive tau-negative neuronal and glial inclusions in the most common form of frontotemporal lobar degeneration (FTLD) and in amyotrophic lateral sclerosis (ALS). It was demonstrated that different TDP-43 profiles correspond to clinical phenotypes of FTLD or ALS subgroups, and the differential diagnostic potential of TDP-43 was suggested.


OBJECTIVE
To examine TDP-43 in cerebrospinal fluid (CSF) and to analyze whether it could serve as a diagnostic marker.


METHODS
We characterized CSF TDP-43 by immunoblot using different TDP-43 antibodies and determined the relative TDP-43 levels in CSF samples from patients.


METHODS
Academic research.


METHODS
Twelve patients with FTLD, 15 patients with ALS, 9 patients with ALS plus FTLD, 3 patients with ALS plus additional signs of frontal disinhibition, and 13 control subjects.


METHODS
Results of TDP-43 immunoblot.


RESULTS
Polyclonal TDP-43 antibodies recognized a 45-kDa band in all analyzed samples. Two monoclonal and N-terminus-specific antibodies did not detect any specific bands, but C-terminus-specific antibodies detected a 45-kDa band and additional bands at approximately 20 kDa in all CSF samples. Relative quantification of 45-kDa bands revealed significant differences among the diagnostic groups (P =.046). Specifically, patients with ALS (P =.03) and FTLD (P =.02) had higher TDP-43 levels than controls but with a prominent overlap of values.


CONCLUSIONS
Although there is no evidence of pathologically altered TDP-43 proteins in CSF, TDP-43 levels in CSF might aid in characterizing subgroups of patients across the ALS and FTLD disease spectrum.
Steinacker
Petra
P
Department of Neurology, University of Ulm, Ulm, Germany.
Hendrich
Corinna
C
Sperfeld
Anne D
AD
Jesse
Sarah
S
von Arnim
Christine A F
CA
Lehnert
Stefan
S
Pabst
Alice
A
Uttner
Ingo
I
Tumani
Hayrettin
H
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
Kretzschmar
Hans A
HA
Ludolph
Albert
A
Neumann
Manuela
M
Otto
Markus
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis* / Q000523:psychology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004268:DNA-Binding Proteins / Q000134:cerebrospinal fluid*; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D004268:DNA-Binding Proteins