THE CANINE AS AN ANIMAL-MODEL OF HUMAN AGING AND DEMENTIA

The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning, memory and other cognitive functions. Cani nes develop extensive beta-amyloid deposition within neurons and their synaptic fields, which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular changes, dilati on of the ventricles, and cytoskeletal changes. Neurofibrillary tangle s (NFTs) are not present in the aged canine. Thus, the aged canine bra in provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported b y behavioral data. We have found that the extent of beta-amyloid depos ition correlates with a decline in select measures of cognitive functi on. These data provide the first evidence of a correlation between bet a-amyloid accumulation and cognitive decline in the absence of NFTs. W e summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropa thology similar to that observed in aged humans; (b) Veterinarians hav e observed that many canines exhibit a clinical syndrome of age-relate d cognitive dysfunction; (c) Aged canines are deficient on a variety o f neuropsychological tests of cognitive function; (d) The level of bet a-amyloid accumulation correlates with cognitive dysfunction in the ca nine. These data indicate that the aged canine is a particularly usefu l model for studying age-related cognitive dysfunction (ARCD), early n euronal changes associated with aging, and the initial stages of senil e plaque formation.