Abstract
Background
Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are incurable, progressive and fatal neurodegenerative diseases with patients variably affected clinically by motor, behavior, and cognitive deficits. The accumulation of an RNA-binding protein, TDP-43, is the most significant pathological finding in approximately 95% of ALS cases and 50% of FTD cases, and discovery of this common pathological signature, together with an increasing understanding of the shared genetic basis of these disorders, has led to FTD and ALS being considered as part of a single disease continuum. Given the widespread aggregation and accumulation of TDP-43 in FTD-ALS spectrum disorder, TDP-43 may have potential as a biomarker in these diseases.
Methods
We therefore conducted a systematic review and meta-analysis to evaluate the diagnostic utility of TDP-43 detected in the cerebrospinal fluid (CSF) of patients with FTD-ALS spectrum disorder.
Results
From seven studies, our results demonstrate that patients with ALS have a statistically significantly higher level of TDP-43 in CSF (effect size 0.64, 95% CI: 0.1–1.19, p = 0.02).
Conclusions
These data suggest promise for the use of CSF TDP-43 as a biomarker for ALS.
Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are incurable, progressive and fatal neurodegenerative diseases with patients variably affected clinically by motor, behavior, and cognitive deficits. The accumulation of an RNA-binding protein, TDP-43, is the most significant pathological finding in approximately 95% of ALS cases and 50% of FTD cases, and discovery of this common pathological signature, together with an increasing understanding of the shared genetic basis of these disorders, has led to FTD and ALS being considered as part of a single disease continuum. Given the widespread aggregation and accumulation of TDP-43 in FTD-ALS spectrum disorder, TDP-43 may have potential as a biomarker in these diseases.
Methods
We therefore conducted a systematic review and meta-analysis to evaluate the diagnostic utility of TDP-43 detected in the cerebrospinal fluid (CSF) of patients with FTD-ALS spectrum disorder.
Results
From seven studies, our results demonstrate that patients with ALS have a statistically significantly higher level of TDP-43 in CSF (effect size 0.64, 95% CI: 0.1–1.19, p = 0.02).
Conclusions
These data suggest promise for the use of CSF TDP-43 as a biomarker for ALS.
| Original language | English |
|---|---|
| Article number | 90 |
| Number of pages | 7 |
| Journal | BMC Neurology |
| Volume | 18 |
| Early online date | 28 Jun 2018 |
| DOIs | |
| Publication status | Published - Jun 2018 |
Bibliographical note
The work was funded by the Future-MND grant. Grant code: 217ARF R43969,3138. Grant holder SP.
Data Availability Statement
All data are available within the text of the manuscript.Keywords
- TDP-43
- Amyotrophic lateral sclerosis
- Systematic review
- Biomarker
- Meta-analysis