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

ABSTRACT: 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-? (A?)42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for A? deposition in brain. However, the relevance of CSF A? levels prior to deposition is not entirely known. Dogs are similar to man with respect to amyloid-? protein precursor (A?PP)-processing, age-related amyloid plaque deposition, and cognitive dysfunction. In the current study, we evaluated the relation between CSF A?42 levels and cognitive performance in young to middle-aged dogs (1.5-7 years old). Additionally, CSF sA?PP? and sA?PP? were measured to evaluate A?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?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? concentrations coincided with low or high sA?PP?, sA?PP?, and CXCL-1 levels, respectively. Dogs with high A? concentrations showed significant learning impairments on delayed non-match to position (DNMP), object discrimination, and reversal learning compared to dogs with low A? concentrations. Our data support the hypothesis that high levels of CSF A? 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.

SUBMITTER: Borghys H 

PROVIDER: S-EPMC5271428 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature