Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis
Abstract
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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Increased levels of TDP-43 in CSF have been detected in patients with ALS and FTD.
“Increased levels of TDP-43 in CSF have been detected in patients with ALS351,352 and FTD.352”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [351]
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- Authors
- Kasai, T., Tokuda, T., Ishigami, N., Sasayama, H., Foulds, P., Mitchell, D. J., Mann, D. M. A., Allsop, D., & Nakagawa, M.
- Affiliations
- Kyoto Prefectural University of Medicine (JP)
- Lancaster University (GB)
- Royal Preston Hospital (GB)
- University of Manchester (GB)
- Corresponding author
- Tokuda, Takahiko
- Venue
- Acta Neuropathologica
- Published
- 2008-11-07
- Volume
- 117
- Issue
- 1
- Pages
- 55-62
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2164591900
- Cited by
- 211
- References
- 35
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 12 · 2023: 11 · 2022: 7 · 2021: 16 · 2020: 8 · 2019: 11 · 2018: 15 · 2017: 7 · 2016: 13 · 2015: 12 · 2014: 9 · 2013: 15 · 2012: 16
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- TDP-43, amyotrophic lateral sclerosis, cerebrospinal fluid, biomarkers, early diagnosis, sporadic ALS, TDP-43 aggregation, ELISA quantification, disease onset timing
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Severity of Illness Index, Time Factors, Biomarkers
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