Detection and Quantification of β-Amyloid, Pyroglutamyl Aβ, and Tau in Aged Canines

Abstract

Canine cognitive dysfunction syndrome is an age-associated disorder that resembles many aspects of human Alzheimer disease. The characterization of canine cognitive dysfunction syndrome has been restricted to selected laboratory dogs and mongrels, thereby limiting our knowledge of potential breed-related and age-related differences. We examined the brains of 24 dogs from various breeds. The frontal cortex, hippocampus, and entorhinal cortex were investigated. Deposits of β-amyloid (Aβ) and tau were analyzed phenotypically and quantified stereologically. In all dogs aged 10 years or older, plaques containing pyroglutamyl Aβ and Aβ8-17 were detected. Within the ventral hippocampus, significantly more pyroglutamyl Aβ plaques were deposited in small and medium dogs than in large dogs. Hyperphosphorylated tau with formation of neurofibrillary tangles was observed in 3 animals aged 13 to 15 years. This study provides the first investigation of pyroglutamyl Aβ in comparison with total Aβ (as shown by Aβ8-17 immunoreactivity) in dogs of different breeds, sizes, and ages. Our results indicate that canine cognitive dysfunction syndrome is relatively common among aged canines, thereby emphasizing the relevance of such populations to translational Alzheimer disease research.

Translational models for vascular cognitive impairment: a review including larger species

“…Cognitive impairment was evident on measures reflecting learning and memory, and a subset of aged animals became severely impaired [41, 42]. A strength of the model is that Aβ, critically involved with plaque accumulation and cerebral amyloid angiopathy (CAA), is very similar in dogs and humans [117–119]. Vascular and perivascular abnormalities and cerebrovascular Aβ pathology are frequently found in aged dogs [40, 120–124].…”

An N-terminal motif unique to primate tau enables differential protein–protein interactions

“…Interestingly, there are reports of human-like AD and tau pathology in dogs (45,46), while AD mouse models with Aβ do not develop human-like tau pathology (i.e. NFTs) unless human tau is coexpressed (47).…”

Alzheimer’s disease: experimental models and reality

“…Aged dogs have the same Aβ sequence as humans and they develop plaques and CAA starting at 8–9 years of age[137, 143, 148]. Plaques first develop in the prefrontal cortex and later in the temporal and occipital cortices, following a similar, but not identical, pattern to humans.…”

“…Other neuropathological features present in aged dogs include cortical atrophy, declined ratio of CSF Aβ42:40, increased Aβ oligomers, and presence of oxidative damage and mitochondrial dysfunction [16]. NFTs are typically not observed; however, pretangles and possible NFTs have been observed in a very limited number of aged, demented dogs [137, 148]. In addition, synaptosomes from demented dogs contain increased total and phosphorylated tau than non-demented dogs, suggesting that cognitive impairment in aged dogs may result from synaptic impairment [148].…”