Exosomal TAR DNA binding protein 43 profile in canine model of amyotrophic lateral sclerosis: a preliminary study in developing blood-based biomarker for neurodegenerative diseases. (31st December 2023)

• Record Type: Journal Article
• Authors: Pfeiffer, Penelope; Coates, Joan R.; Esqueda, Yajaira M.; Kennedy, Andrew; Getchell, Kyleigh; McLenon, Myra; Kosa, Edina; Agbas, Abdulbaki
• Is Part Of: Annals of medicine. Volume 55:Number 1(2023)
• Page Start: 34
• Page End: 41
• Publication Date: 2023-12-31
• Subjects: TDP-43 -- amyotrophic lateral sclerosis -- degenerative myelopathy -- exosome -- biomarker; Medicine -- Periodicals; 610
• DOI: 10.1080/07853890.2022.2153162
• Languages: English
• ISSNs: 0785-3890

Abstract

Abstract: Objective: Blood-based biomarkers provide a crucial information in the progress of neurodegenerative diseases with a minimally invasive sampling method. Validated blood-based biomarker application in people with amyotrophic lateral sclerosis would derive numerous benefits. Canine degenerative myelopathy is a naturally occurring animal disease model to study the biology of human amyotrophic lateral sclerosis. Serum derived exosomes are potential carriers for cell-specific cargoes making them ideal venue to study biomarkers for a variety of diseases and biological processes. This study assessed the exosomal proteins that may be assigned as surrogate biomarker that may reflect biochemical changes in the central nervous system. Methods: Exosomes were isolated from canine serum using commercial exosome isolation reagents. Exosomes target proteins contents were analyzed by the Western blotting method. Results: The profiles of potential biomarker candidates in spinal cord homogenate and that of serum-derived exosomes were found elevated in dogs with degenerative myelopathy as compared to control subjects. Conclusions: Serum-derived exosomal biomolecules can serve as surrogate biomarkers in neurodegenerative diseases. KEY MESSAGES: A canine with degenerative myelopathy can serve as a model animal to study human amyotrophic lateral sclerosis. Serum-derived exosomes contain Transactive Response DNA Binding Protein 43 (TDP-43), a potential biomarker candidate. The levels of spinal cord TDP-43 proteins and that of serum-derived exosomes exhibited similar profiling. Therefore, serum derived exosomes may be used as a venue for establishing blood-based biomarkers for neurodegenerative diseases.