β-Amyloid Accumulation Correlates with Cognitive Dysfunction in the Aged Canine

It is well known that β-amyloid accumulates abnormally in Alzheimer's disease; however, β-amyloid's relationship to cognitive dysfunction has not been clearly established and is often confounded by the presence of neurofibrillary tangles. We used canines to investigate the relationship between β-amyloid accumulation and cognitive function in an animal model of aging lacking neurofibrillary tangles. The performance of 20 canines (11 purebred beagles and 9 mongrels) on a battery of six cognitive tasks was measured. These tasks included Reward Approach and Object Approach learning, as well as Discrimination, Reversal, Object Recognition, and Spatial learning and memory. Aged canines were impaired on some tasks but not others. β-Amyloid-immunopositive plaques were found in many of the older animals. Plaques were all of the diffuse subtype and many contained intact neurons detected with double-labeling for neurofilaments. No neurofibrillary tangles were detected. β-Amyloid was also associated with the processes of many neurons and with blood vessels. Using computerized image analysis, we quantified the area occupied by β-amyloid in entorhinal cortex, frontal cortex, and cerebellum. Controlling for age-related increases in β-amyloid, we observed that increased β-amyloid deposition is strongly associated with deficits on Discrimination learning (r= .80), Reversal learning (r= .65), and Spatial learning (r= .54) but not the other tasks. There were a few differences between breeds which are discussed in the text. Overall, these data suggest that β-amyloid deposition may be a contributing factor to age-related cognitive dysfunction prior to the onset of neurofibrillary tangle formation.