Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Since 1998, California sea lion (Zalophus
californianus) stranding events associated with domoic
acid toxicosis (DAT) have consistently increased. Outside of direct
measurement of domoic acid in bodily fluids at the time of stranding,
there are no practical nonlethal clinical tests for the diagnosis
of DAT that can be utilized in a rehabilitation facility. Proteomics
analysis was conducted to discover candidate protein markers of DAT
using cerebrospinal fluid from stranded California sea lions with
acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005
protein families were identified experiment-wide. A total of 83 proteins
were significantly different in abundance across the three groups
(adj. p < 0.05). MDH1, PLD3, ADAM22, YWHAG, VGF,
and CLSTN1 could discriminate California sea lions with or without
DAT (AuROC > 0.75). IGKV2D-28, PTRPF, KNG1, F2, and SNCB were able
to discriminate acute DAT from chronic DAT (AuROC > 0.75). Proteins
involved in alpha synuclein deposition were over-represented as classifiers
of DAT, and many of these proteins have been implicated in a variety
of neurodegenerative diseases. These proteins should be considered
potential markers for DAT in California sea lions and should be prioritized
for future validation studies as biomarkers.