Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis

被引:0
作者
Takashi Kasai
Takahiko Tokuda
Noriko Ishigami
Hiroshi Sasayama
Penelope Foulds
Douglas J. Mitchell
David M. A. Mann
David Allsop
Masanori Nakagawa
机构
[1] Kyoto Prefectural University of Medicine,Department of Neurology
[2] Lancaster University,Division of Biomedical and Life Sciences, School of Health and Medicine
[3] Royal Preston Hospital,MND Care and Research Centre
[4] University of Manchester,Clinical Neurosciences Research Group, School of Translational Medicine, Faculty of Medical and Human Sciences
[5] Greater Manchester Neurosciences Centre,undefined
[6] Hope Hospital,undefined
来源
Acta Neuropathologica | 2009年 / 117卷
关键词
Amyotrophic lateral sclerosis; TDP-43; Cerebrospinal fluid; ELISA; Biomarker;
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摘要
There is mounting pathological, biochemical and genetic evidence that the metabolism and aggregation of the 43-kDa transactive response (TAR)-DNA-binding protein (TDP-43) play a crucial role in the pathogenesis of sporadic and some forms of familial amyotrophic lateral sclerosis (ALS). Recently, it was reported using an ELISA system that elevated levels of TDP-43 were detected in plasma samples from patients with Alzheimer’s disease and frontotemporal dementia, compared to healthy controls. To determine whether quantification of TDP-43 in cerebrospinal fluid (CSF) is potentially informative in the diagnosis of ALS, we measured the concentration, by a similar ELISA method, of TDP-43 in CSF from 30 patients with ALS (diagnosed according to the revised El Escorial criteria) and 29 age-matched control patients without any neurodegenerative disease. We found that, as a group, the ALS patients had significantly higher levels of TDP-43 in their CSF than the age-matched controls (6.92 ± 3.71 ng/ml in ALS versus 5.31 ± 0.94 ng/ml in controls, p < 0.05), with levels of TDP-43 in CSF elevated beyond 95% upper confidence level for the control group in six (20%) of the patients with sporadic ALS. All the six patients with higher levels of CSF TDP-43 were examined within 10 months of the onset of illness. The patients examined within 10 months of onset showed significantly higher levels of CSF TDP-43 (8.24 ± 4.72 ng/ml) than those examined after 11 months or more of onset (5.41 ± 0.66 ng/ml, p < 0.05). These results suggest that the levels of TDP-43 in CSF may increase in the early stage of ALS. We also confirmed the existence of the TDP-43 protein in CSF from some patients with ALS, and a control subject, by western blotting of proteins immunocaptured from the CSF samples. Raised TDP-43 levels in the CSF may preempt the formation of TDP-43 pathology in the central nervous system, or correlate with early-stage TDP-43 pathology, and accordingly be a biomarker for the early stage of ALS.
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页码:55 / 62
页数:7
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