The Canine (Dog) Model of Human Aging and Disease: Dietary, Environmental and Immunotherapy Approaches

摘要

Abstract. Aged dogs (beagles) develop losses in executive function, learning and memory. The severity of decline in thesencognitive domains represents a spectrum that captures normal aging, mild cognitive impairment and early/mild Alzheimer’sndisease (AD) in humans. In parallel, dogs naturally accumulate several types of neuropathology (although not all) consistentnwith human brain aging and AD including cortical atrophy, neuron loss, loss of neurogenesis, amyloid-β (Aβ) plaques, cerebralnamyloid angiopathy and oxidative damage. Many of these neuropathological features correlate with the extent of cognitivendecline in a brain region-dependent manner. Dogs are ideally suited for longitudinal studies, and we provide a summary of thenbeneficial effects of an antioxidant diet, behavioral enrichment, and Aβ immunotherapy. In addition, combinatorial treatmentnapproaches can be a powerful strategy for improving brain function through enhancement of multiple molecular pathways.