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Abstract
Aim: 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.
Authors contributions
A Agbas performed study concept and design. Acquisition of data was done by R Wilhite, J Sage, A Bouzid, T Primavera and A Agbas. A Agbas performed analysis,, interpretation of data, and drafting of manuscript.
Acknowledgements
A Agbas acknowledges the contributions of the student research fellows of College of Osteopathic Medicine. We are grateful for E Vidoni and K Newman, and KU Medical Center bio-repository facilities for providing brain tissues and platelet lysates. We are thankful for E Agbas for editing process of this manuscript. For information on the data used in Figure 1, please contact [email protected]
Financial & competing interests disclosure
Research reported in this publication was supported by several pilot project funds from QS85523J, University of Kansas Medical Center Research Institute, Inc. (QS85523J), FONTIERS-Trail Blazer Award (01–2429–001) and KCU intramural grants. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.