New preclinical biomarkers for prion diseases in the cerebrospinal fluid proteome revealed by mass spectrometry

This study addresses the urgent need for preclinical biomarkers of prion diseases, which currently can only be diagnosed in advanced stages when neurodegeneration is irreversible. Using mass spectrometry, the cerebrospinal fluid (CSF) proteome of sheep with natural scrapie was analyzed, including preclinical, clinical, and healthy animals. Forty-six proteins significantly altered in the preclinical stage (p < 0.01) were identified, associated with stress and inflammatory responses. Five proteins were validated using ELISA: SYNCRIP (nucleic acid metabolism), PLD3 and CTSD (lysosomal apoptosis), C4 (classical immune response), and SPP1 (a proinflammatory cytokine). These proteins showed increased levels in the preclinical phase, with CTSD returning to baseline levels in the clinical group. These findings provide promising candidates for preclinical biomarker development in prion diseases, with ongoing research to confirm their potential utility.