Young to Middle-Aged Dogs with High Amyloid-β Levels in Cerebrospinal Fluid are Impaired on Learning in Standard Cognition tests

Understanding differences in Alzheimer's disease biomarkers before the pathology becomes evident can contribute to an improved understanding of disease pathogenesis and treatment. A decrease in amyloid-beta (A beta) 42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for A beta deposition in brain. However, the relevance of CSF A beta levels prior to deposition is not entirely known. Dogs are similar to man with respect to amyloid-beta protein precursor (A beta PP)-processing, age-related amyloid plaque deposition, and cognitive dysfunction. In the current study, we evaluated the relation between CSFA beta(42) levels and cognitive performance in young to middle-aged dogs (1.5-7 years old). Additionally, CSF sA beta PP alpha and sA beta PP beta were measured to evaluate A beta PP processing, and CSF cytokines were measured to determine the immune status of the brain. We identified two groups of dogs showing consistently low or high CSF A beta(42) levels. Based on prior studies, it was assumed that at this age no cerebral amyloid plaques were likely to be present. The cognitive performance was evaluated in standard cognition tests. Low or high A beta concentrations coincided with low or high sA beta PP beta, sA beta PP beta, and CXCL-1 levels, respectively. Dogs with high A beta concentrations showed significant learning impairments on delayed non-match to position (DNMP), object discrimination, and reversal learning compared to dogs with low A beta concentrations. Our data support the hypothesis that high levels of CSF A beta in dogs coincide with lower cognitive performance prior to amyloid deposition. Further experiments are needed to investigate this link, as well as the relevance with respect to Alzheimer's disease pathology progression.