Conclusion
Risks for age-related AD and CCD are a complicated interplay between aging, genetic risk factors and environmental influences. CCD in dogs is similar to human AD with respect to APP processing, amyloid plaque deposition and cognitive dysfunction. As dogs age, they have been shown to accumulate amyloid plaques, but, dissimilar to human AD patients, dog brain rarely contains NFTs. Aβ peptide accumulates in the canine brain extracellular space in the form of soluble oligomers, fibrils and Aβ plaques. Its toxic accumulation is believed to be responsible for the neuronal dysfunction and degeneration although the severity of the disease does not always correlate with amyloid burden, but might correlate with toxic fibril polymorphs.
Dogs over 7–8 years seem to be interesting, naturally occurring model organism for aging/dementia that fairly faithfully recapitulate human disease. They are potentially much more useful as rodent models as in laboratory rodents neurodegenerative diseases do not occur spontaneously. Furthermore, genetically modified mice used in research often show very different neurodegeneration courses, as seen in humans. Dogs also spontaneously develop vasculopathies, such as CAA, and perhaps vascular dementia although this has not yet been truly studied, and are therefore also valuable as models to decipher the age and/or dementia related cerebrovascular changes that often accompany or even precede neurodegeneration in human patients.
There are no effective treatments for neurodegenerative disorders, practically all currently available treatments are symptomatic. This is partially related to the poor understanding of the pathogenesis of these diseases, and partly due to the lack of good animal models. Cholinesterase or secretase inhibitor therapy or immunotherapy has been attempted in dogs with CDD, with overlapping results to human AD trials. The neuroprotective effects of cognitive enrichment, alongside with antioxidant-rich diet, show benefits in managing the disease progression and severity in both humans and dogs. Similar results with various drugs do suggest that dogs are useful model to study both pathogenesis and novel treatments for AD in the future.
Taken together, animal studies are important to dissect the molecular and cellular processes specific to AD pathology. Dogs with CCD not only develop isomorphic changes in human cognition and brain pathology, but also accurately predicted the efficacy of known AD treatments and would be therefore good models for testing new substances that affect the lowering of Aβ levels or the reduction or degradation of aggregates associated with AD. This would benefit human patients, but could also help dog patients as any successful treatments could be also introduced into clinical veterinary medicine with the aim to successfully treat this debilitating disease in canine patients.