Investigation of Serum Neurofilament Light Chain as a Surrogate for Cerebrospinal Fluid Neurofilament Light Chain in Canine Cognitive Dysfunction Syndrome

The serum neurofilament light chain (NfL) is a promising circulating biomarker for canine cognitive dysfunction syndrome (CCDS). This cross-sectional study evaluated serum NfL (sNfL) as a surrogate for cerebrospinal fluid NfL (cNfL) and assessed the effects of physiological factors on its clinical utility. Biofluid NfL was analyzed using the single-molecule array (Simoa) across 126 clinical samples, comprising 44 cNfL and 25 paired cNfL/sNfL samples in geriatric dogs (>8 years) and 16 paired samples from a younger cohort (≤8 years). A moderate monotonic correlation was observed between cNfL and sNfL in geriatric dogs, but this association was not maintained in the younger cohort after adjusting for body weight. In the geriatric cohort, raw sNfL levels differentiated cerebral atrophy from controls but not from other intracranial pathologies. Notably, the ability of cNfL to discriminate structural, atrophic, and mixed brain pathologies from controls significantly improved after adjustment for confounding effects of age and body weight. A similar optimization strategy may be applicable to sNfL. Systematically controlling for these physiological covariates in larger cohorts could potentially further improve the diagnostic precision of blood-based NfL screening in primary veterinary practice.