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load and increasing age, but not all studies can  nd a positive correlation to the degree of cognitive decline. The same discrepancy has been demonstrated between studies investigating the association of neuropathological features and cognition in humans suffering from AD. Accumulation of hyperphosphorylated tau protein
inside the neurons leading to neuro brillary tangles
and neuronal death is one of the other pathological hallmarks in human AD. In the aging dog brain, neuro brillary tangles have not been demonstrated although few studies have demonstrated a presence of phosphorylated tau inside the neurons. This may indicate some kind of pre-tangle tau pathology. The reason for the presumed lack of neuro brillary tangles in the canine brain has not yet been fully clari ed. The issue whether neuroin ammation is involved in the pathogenesis related to CCD is sparsely documented. Very few studies have investigated a potential glia-mediated in ammatory response in the aging dog brain and with con icting results.
Comparative aspects to early stage Alzheimer’s disease
The clinical phenotype and progression pattern described for affected dogs are very similar to the
clinical features described for humans suffering from AD dementia. Furthermore, the most striking similarity to AD neuropathology is the characteristics of the extensive
Aβ deposition. Accordingly, the dog is considered
a promising spontaneous model for the Aβ related pathology associated with early stage AD and human brain aging. The presently used transgenic rodent models of AD are seen as mechanistic models. These animal models have contributed signi cantly to the current knowledge of the neuropathology associated with AD, and they are nothing less than essential in translational AD research and in the drug development phase. However, modelling the impact of environmental factors and the complex cognition of humans is challenging in such animal models. The fact that the companion dogs can now be studied as a spontaneous animal model for early Alzheimer’s disease has therefore been welcomed into the scienti c world. Through research, the hope is that we in future will know more about the phenotype, clinical course, and pathophysiology of CCD.
Cotman, C. W., & Head, E. (2008). The canine (dog) model of human aging and disease: Dietary, environmental and immunotherapy approaches. Journal of Alzheimer’s Disease, 15(4), 685–707.
Fast, R., Schutt, T., Toft, N., Moller, A., & Berendt, M. (2013). An observational study with long-term follow-up of canine cognitive dysfunction: clinical characteristics, survival, and risk factors. Journal of Veterinary Internal Medicine, 27(4), 822–829.
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Schutt, T., Helboe, L., Pedersen, L. O., Waldemar, G., Berendt, M., & Pedersen, J. T. (2016). Dogs with Cognitive Dysfunction as a Spontaneous Model for Early Alzheimer’s Disease: A Translational Study of Neuropathological and In ammatory Markers. Journal of Alzheimer’s Disease: JAD, 52(2), 433–449.
Schutt, T., Toft, N., & Berendt, M. (2015). Cognitive Function, Progression of Age-related Behavioral Changes, Biomarkers, and Survival in Dogs More Than 8 Years Old. Journal of Veterinary Internal Medicine / American College of Veterinary Internal Medicine, 29(6), 1569–1577.
Schütt, T., Toft, N., & Berendt, M. (2015). A comparison of 2 screening questionnaires for clinical assessment of canine cognitive dysfunction. Journal of Veterinary Behavior: Clinical Applications and Research, 10(6), 452–458.
Yu, C.-H., Song, G.-S., Yhee, J.-Y., Kim, J.-H., Im, K.-S., Nho, W.-G., ... Sur, J.- H. (2011). Histopathological and Immunohistochemical Comparison of the Brain of Human Patients with Alzheimer’s Disease and the Brain of Aged Dogs with Cognitive Dysfunction. Journal of Comparative Pathology, 145(1), 45–58.
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