Plasma and cerebrospinal fluid biomarkers in aged dogs with cognitive decline

Background: Canine cognitive dysfunction syndrome (CCD) is a naturally occurring progressive neurodegenerative disease that commonly affects geriatric dogs, with age being the primary risk factor. CCD presents a valuable model for studying aging and neurodegeneration due to natural development of the disease and similarities to Alzheimer’s disease (AD). In this study, we evaluated biomarkers that are relevant for human neurodegeneration, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid-beta and the amyloid-beta (Aβ_{1−42/1−40}) ratio, to explore the differences between healthy aging and CCD. Results: Our results demonstrate significant associations between age and dementia biomarkers, with reduced Aβ_{1−42/1−40} ratios in plasma, and elevated NfL levels in cerebrospinal fluid (CSF) at older ages. These biomarkers were also associated cognitive impairment, as assessed by owner-directed CCD surveys. Notably, NfL levels in plasma showed a strong positive correlation with both age and cognitive decline, suggesting its potential utility as a non-invasive diagnostic tool for CCD. While plasma NfL is promising, it is non-specific and can also be elevated due to other neurological conditions. Therefore, combining NfL with other biomarkers, such as GFAP and Aβ, alongside clinical assessments, may enable a more accurate diagnosis of CCD. Conclusion: Our findings further support the use of dogs with CCD as a model for studying AD biomarkers, with implications for the development of therapeutic interventions in both dogs and humans.