Dogs with canine counterpart of Alzheimer's disease lose noradrenergic neurons

Abstract 

Degeneration of noradrenergic neurons in the locus ceruleus is a well-described feature of Alzheimer's disease (AD). In spite of extensive utilization of the dog as a model for human degenerative diseases, there is no data on the response to aging of the noradrenergic system in dogs. We have used modern unbiased stereology to estimate the total number of A6–A7 noradrenergic neurons in normal, aged dogs and dogs with the canine counterpart of AD. In small-breed dogs with no cognitive impairments, the total mean number of tyrosine hydroxylase immunolabeled A6–A7 neurons was 17,228±1655, with no differences between young and aged dogs. In contrast, aged dogs with cognitive impairments exhibited a significant reduction in the total number of A6–A7 neurons (13,487±1374; P=0.001). Additionally, we found a negative correlation between the number of A6–A7 neurons and the extent of β-amyloid deposits in the prefrontal cortex. These results suggest that the canine model could be useful in exploring the potential benefits of noradrenergic drugs for the treatment of AD.

Keywords: Amyloid-beta, Unbiased stereology, Aging, Locus ceruleus, A6–A7, Tyrosine hydroxylase, Gyrus proreus