Age‐related changes in clinically relevant biomarkers in a Beagle model of Alzheimer’s disease.

Abstract Background Canine aging is associated with cognitive decline linked to several neuropathological changes that parallel those reported in Alzheimer’s disease including deposition of amyloid‐β, cerebral amyloid angiopathy, dystrophic neurites, reduced neurogenesis, neuronal loss, activated microglia and astrogliosis. Dogs also demonstrate domain specific cognitive decline with short‐term working memory and executive function impacted early in canine aging. One contributing factor of Alzheimer’s disease is neuroinflammation, including activation of microglia and astrocytes, which are also seen in canine brain aging. Microglia bind to soluble amyloid‐β oligomers and fibrils by various receptors including toll‐like receptors (TLR2, TLR4, TLR6 and TLR8), which is postulated to be part of the neuroinflammatory process in Alzheimer’s disease. Toll like receptor activation leads to downstream production and release of pro‐inflammatory cytokines through the NFκB signaling pathway. Activated astrocytes accumulate around senile plaques and release cytokines, and other cytotoxic molecules, when exposed to amyloid‐b, further contributing to the neuroinflammatory response. The current study sought to investigate whether concentrations of the following cytokines varied by age in canine biofluids; IL‐6, TNFα, IL‐8, IL‐10, and IL‐12. Method Concentrations of the aforementioned cytokines in cerebrospinal fluid and plasma from three age groups of dogs were evaluated in the current study. The young aged group included samples from dogs under 6 years of age. The middle age group included samples from dogs between 6 and 10 years of age. The aged or senior group included samples from dogs greater than 10 years of age. Results and Conclusion The results of the study will be presented, and we hypothesize that age‐related changes in cytokine concentrations may be used as a potential clinically relevant biomarker for evaluating the effects of putative Alzheimer’s disease therapeutics targeting neuroinflammation, particularly when used in conjunction with neuropsychological cognitive assays.