Exosome TDP-43 profile in canine model of ALS: A preliminary study in developing surrogate biomarker

Abstract

AbstractBlood-based biomarkers are considered non-invasive and have the potential to be cost effective. Validated blood-based biomarker application in people with amyotrophic lateral sclerosis (ALS) would derive numerous benefits. Canine degenerative myelopathy (DM) is a animal disease model to study the biology of human ALS. Serum derived exosomes are potential carriers for cell-specific cargoes of proteins, lipids, and genetic materials making them ideal biomarkers for a variety of diseases and biological processes. This study examined the exosomal trans active response DNA binding protein 43 kDa (TDP-43). The TDP-43 pattern as a surrogate biomarker that reflects biochemical changes in central nervous system. Exomes were isolated from canine serum using commercial exosome isolation reagents. TDP-43 and SOD1 profiles in spinal cord homogenate lysate and that of serum-derived exosomes were found elevated in dogs with DM. The authors concluded that levels of spinal cord TDP-43 and serum-derived exosomes were similar in TDP-43 profiling Further investigations are warranted to establish the disease sensitivity and specificity of the exosomal TDP-43 profile as a blood-based biomarker in canine DM.