Platelet phosphorylated TDP-43: An exploratory study for a peripheral surrogate biomarker development for Alzheimer’s disease

Abstract

Aim: Alzheimers disease (AD) and other forms of dementia create a non-curable disease population in Worlds 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 post-mortem brain tissue and platelets of AD and control subjects. Results: We observed an increased TDP-43 (<60%) in post-mortem AD brain regions and similar trends were also observed in patients 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.\n\nLay abstractIn this study, we explore to identify an Alzheimers disease-selective phospho-specific antibody that recognizes the diseased form of TDP-43 protein in patients blood-derived platelets. Our results suggest that selective anti-phosphorylated TDP-43 antibody discriminates Alzheimers disease 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 Alzheimers disease.