Evaluation of some biomarkers for the diagnosis of Canine Cognitive Dysfunction Syndrome

The aim of this study was to investigate the alterations in serum concentrations of Neurofilament Light Chain (NFL), Phosphorylated Tau (p-Tau), Brain-Derived Neurotrophic Factor (BDNF), and Beta-Secretase 1 (BACE1) across different clinical stages of Canine Cognitive Dysfunction Syndrome (CCDS) in geriatric dogs, and to evaluate the potential utility of these biomarkers in early diagnosis. The study population consisted of 75 dogs aged 7 years and older, representing various breeds and sexes. The animals were classified according to the Canine Dementia Scale (CADES) scoring system into the following groups: Healthy Control (n=15), Normal Aging, Mild Cognitive Impairment, Moderate Cognitive Impairment, and Severe Cognitive Impairment. Serum concentrations of NFL, p-Tau, BDNF, and BACE1 were measured using dog-specific ELISA kits, while hematological and blood gas parameters were analyzed using an automated analyzer. The results demonstrated that all evaluated biomarkers (NFL, p-Tau, BDNF, and BACE1) were significantly elevated in the "Mild Cognitive Impairment" group—representing the early stage of CCDS—compared with the control group (p<0.05). However, in the "Severe Cognitive Impairment" group, biomarker concentrations—particularly BDNF and NFL—declined and approached values similar to those of the control group. Strong positive correlations were observed among the biomarkers themselves (p<0.01), although no linear relationship was found between biomarker levels and the clinical Total Score. Additionally, the CADES items related to sleep–wake cycle disturbances and aimless wandering were identified as highly discriminative for diagnosis. In conclusion, serum NFL, p-Tau, BDNF, and BACE1 appear to serve as robust "state markers" reflecting neuronal damage and amyloidogenic processes in the early stages of CCDS (mild impairment). The decline observed in advanced stages may be associated with neuronal exhaustion and brain atrophy. When used in conjunction with clinical scoring, these biomarkers provide valuable information for the early detection of CCDS