Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: specificity, sensitivity, and a possible prognostic value.
TAR DNA binding protein of 43 kDa (TDP-43) is likely to be the major pathogenetic protein in amyotrophic lateral sclerosis (ALS). A previous study has shown that levels of TDP-43 in CSF measured by an ELISA are significantly higher for ALS patients than for controls. The aim of this study was to investigate whether elevated CSF TDP-43 levels are specific to ALS, and are associated with clinical profiles in ALS patients. We measured CSF TDP-43 levels by the same ELISA in 27 ALS patients and 50 neurodegenerative or inflammatory disease controls such as Parkinson's disease, multiple sclerosis, and Guillain-Barré syndrome. Results showed that the CSF TDP-43 levels were increased only in ALS patients. Receiver operating characteristic (ROC) analyses showed a sensitivity of 59.3% and a specificity of 96.0%. We also found that lower CSF TDP-43 levels may be associated with shorter survival time. In conclusion, the CSF TDP-43 is a potential biomarker that supports a diagnosis of ALS. Moreover, among ALS patients, lower levels of CSF TDP-43 may reflect the accumulation of TDP-43 in the cortical and spinal motor neurons and thereby shorter survival time, although this should be confirmed in larger prospective studies.
Department of Neurology, Graduate School of Medicine, Chiba University, Japan. y-noto@koto.kpu-m.ac.jp
Yu-Ichi
Y
Noto
Kazumoto
K
Shibuya
Yasunori
Y
Sato
Kazuaki
K
Kanai
Sonoko
S
Misawa
Setsu
S
Sawai
Masahiro
M
Mori
Tomoyuki
T
Uchiyama
Sagiri
S
Isose
Saiko
S
Nasu
Yukari
Y
Sekiguchi
Yumi
Y
Fujimaki
Takashi
T
Kasai
Takahiko
T
Tokuda
Masanori
M
Nakagawa
Satoshi
S
Kuwabara
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004268:DNA-Binding Proteins / Q000134:cerebrospinal fluid*; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity
D015415:Biomarkers; D004268:DNA-Binding Proteins