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Platelet phosphorylated TDP-43: an exploratory study for a peripheral surrogate biomarker development for Alzheimer's disease
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Alzheimer's disease (AD) and other forms of dementia create a noncurable disease population in world's societies. To develop a blood-based biomarker is important so that the remedial or disease-altering therapeutic intervention for AD patients would be available at the early stage. Materials & methods: TDP-43 levels were analyzed in postmortem brain tissue and platelets of AD and control subjects. Results: We observed an increased TDP-43 (<60%) in postmortem AD brain regions and similar trends were also observed in patient's platelets. Conclusion: Platelet TDP-43 could be used as a surrogate biomarker that is measurable, reproducible and sensitive for screening the patients with some early clinical signs of AD and can be used to monitor disease prognosis. Lay abstract: In this study, we explore to identify an Alzheimer's disease (AD)-selective phospho-specific antibody that recognizes the diseased form of TDP-43 protein in patient's blood-derived platelets. Our results suggest that selective antiphosphorylated TDP-43 antibody discriminates AD from non-demented controls and patients with amyotrophic lateral sclerosis. Therefore, platelet screening with a selective antibody could potentially be a useful tool for diagnostic purposes for AD.