The post-translational modification profile of TAR DNA-Binding Protein (TDP-43) in platelets of patients with Alzheimer's disease: An exploratory study for blood-based biomarker development.

Johnson, Q.; Hadjian, M.; Bah, A.; Smith, S.; Kosa, E.; Agbas, A.

doi:10.1101/2023.01.29.526122

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bioRxiv · 10.1101/2023.01.29.526122

The post-translational modification profile of TAR DNA-Binding Protein (TDP-43) in platelets of patients with Alzheimer's disease: An exploratory study for blood-based biomarker development.

Johnson, Q.·Hadjian, M.·Bah, A.·Smith, S.·Kosa, E.·Agbas, A.

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Abstract

The assignment of blood-based biomarkers for neurodegenerative diseases is of great clinical value. Well-developed and validated blood-based biomarkers can serve in early diagnosis and prognosis as well as aid in patient screening when recruiting for clinical trials. We attempted to establish a portfolio for post-translationally modified TAR DNA/RNA-binding protein (TDP-43), a regulator of nuclear transcription, in platelet cytosol obtained from patients with Alzheimers disease (AD) comparing to age-matched healthy subjects and a disease control cohort. We aimed to identify the most prominent post-translational modifications of TDP-43 as an AD-relevant biomarker and to demonstrate that such an assessment can be performed in peripheral blood. We have isolated TDP-43 protein from human platelet cytosol utilizing an Immunoaffinity chromatography. The eluates were immunoprobed with a series of antibodies raised against post-translationally modified proteins. We employed a capillary electrophoretic immunoassay (CEI) to assess the phosphorylated TDP-43 profile. We observed that SUMOylation, phosphorylation, ubiquitination, and cysteine oxidation of TDP-43 are more prominent in platelet cytosol of AD patients as compared to control subjects. These studies will pave the way for identifying disease-specific TDP-43 derivatives that can be potential biomarkers for early diagnosis and the development of therapeutics.

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Johnson, Q., Hadjian, M., Bah, A., Smith, S., Kosa, E., Agbas, A.. 2023-01-30. The post-translational modification profile of TAR DNA-Binding Protein (TDP-43) in platelets of patients with Alzheimer's disease: An exploratory study for blood-based biomarker development.. https://doi.org/10.1101/2023.01.29.526122

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