CSF TAR DNA Binding Protein -43 (TDP-43) As A Potential Biomarker In Diagnosing Amyotrophic Lateral Sclerosis (ALS): A Meta-Analysis

Authors

  • Tirthal Rai , Desy TM , Deepika Kamath M , Varashree Bolar Sooryakant

DOI:

https://doi.org/10.47750/pnr.2022.13.S09.145

Abstract

Background: Mutation of TDP -43 gene may contribute for the development of amyotrophic lateral sclerosis (ALS) and the absolute concentrations of TDP-43 in CSF and plasma have varied across studies, therefore the aim of the study was to assess whether CSF TDP-43 levels could be a potential biomarker for diagnosing ALS and analyze whether p.N345K mutation of TDP-43 is associated with the risk of ALS.

Methods: Online database was thoroughly searched for case-control studies reporting mean and standard deviation of CSF TDP-43 levels in ALS patients and controls. Totally 208 cases and 280 controls for CSF TDP-43 analysis were included.

Results: Cases showed a substantial rise in CSF TDP-43 levels (SMD -1.365 and SE- 0.898 (p=0.000), Confidence interval (-0.3953 to 3.1253). As the SMD> 0, it suggests that CSF TDP-43 is an effective marker for diagnosing ALS. CSF TDP-43 is significantly (p=0.000) associated with the disease with Chi-square =157.238, DF=8. However, in the studies with Q= 61.5376, (p=0.000), significant heterogeneity in impact estimates was found. This implied that CSF played a helpful role. The diamond, which is a visual depiction of the pooled effect estimate, was likewise on the right side of the null effect line, indicating that TDP-43 plays a helpful role in ALS diagnosis. Meta- analysis for the proportion of TDP-43 p.N345K gene shows cumulative odds ratio of 48.06 with a chi-square equal to 15.85 which was highly significant (p = 0.0004). There was no significant heterogeneity (p=0.125) with Q=2.35, DF = 1. Both the studies as well as the diamond were on right side of line of no effect, suggesting that mutation of the TDP-43 p.N345K gene is associated with ALS.

Conclusion: TDP-43 levels in CSF may be a potential biomarker for the diagnosis of ALS. Mutation of TDP-43 p.N345K gene may be associated with the causation of ALS.

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Published

2022-11-16 — Updated on 2022-11-16

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How to Cite

Tirthal Rai , Desy TM , Deepika Kamath M , Varashree Bolar Sooryakant. (2022). CSF TAR DNA Binding Protein -43 (TDP-43) As A Potential Biomarker In Diagnosing Amyotrophic Lateral Sclerosis (ALS): A Meta-Analysis. Journal of Pharmaceutical Negative Results, 1226–1236. https://doi.org/10.47750/pnr.2022.13.S09.145

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