Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Development of a Sensitive and Reliable Immunoassay to Quantify TDP-43 in Human Biofluids

Version 1 : Received: 11 September 2024 / Approved: 12 September 2024 / Online: 12 September 2024 (09:16:06 CEST)

How to cite: An, J.; Gopalakrishnan, L.; Ortega, V.; Saul, J.; Kadali, R.; Bowser, R. Development of a Sensitive and Reliable Immunoassay to Quantify TDP-43 in Human Biofluids. Preprints 2024, 2024090984. https://doi.org/10.20944/preprints202409.0984.v1 An, J.; Gopalakrishnan, L.; Ortega, V.; Saul, J.; Kadali, R.; Bowser, R. Development of a Sensitive and Reliable Immunoassay to Quantify TDP-43 in Human Biofluids. Preprints 2024, 2024090984. https://doi.org/10.20944/preprints202409.0984.v1

Abstract

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43 related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification. In this study, we developed and validated a sensitive immunoassay for the detection of TDP-43 in human biofluids using the Meso Scale Discovery (MSD) platform. We used this immunoassay to quantify TDP-43 levels in the plasma and serum of healthy controls and ALS patients. Our results indicate a reduction of total TDP-43 in the blood of ALS patients compared to healthy controls.

Keywords

TDP-43; immunoassay; MSD; ALS; biomarker; neurodegenerative disease

Subject

Biology and Life Sciences, Neuroscience and Neurology

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