In dogs, formation and maturation of Aβ deposits was observed by immunostaining throughout the canine cortical gray matter layers in a four-stage distribution, which is also characteristic for human AD, and this, according to some studies, correlates with the severity of cognitive deficit in the dog (Bosch et al., 2012) and varies as a function of age and size (weight) in companion dogs (Rofina et al., 2006; Schmidt et al., 2015). The Aβ load was higher in small and medium size dogs, which can be explained by the longer life span of smaller dogs and thus longer time necessary to accumulate these deposits (Schmidt et al., 2015). Most of the studies, on CCD brains, were made on geriatric dogs of different breeds and sizes, hence in this review the pathology is mainly described without further specifications of individual dogs characteristics. The canine prefrontal cortex is normally the site of disease onset (Figure 2), which spreads progressively to the parietal, entorhinal and occipital cortices, and lesions in certain brain regions correlate with certain behavioral deficits, as shown in Table 1. In separate studies amyloid plaques of mainly diffuse type were detected in several regions of canine brain, in the frontal and temporal cortex (Ishihara et al., 1991; Colle et al., 2000; Pugliese et al., 2006; Schmidt et al., 2015; Ozawa et al., 2016; Schütt et al., 2016; Smolek et al., 2016), in entorhinal cortex and hippocampus (Cummings et al., 1993; Colle et al., 2000; Yu et al., 2011; Schmidt et al., 2015; Borghys et al., 2017) and parietal cortex (Yu et al., 2011). Hippocampal deposits of a subspecies of pyroglutamyl Aβ, the highly neurotoxic pE3AA, were also detected in demented dogs (Schmidt et al., 2015). These plaques were more abundant in small and medium dogs (Schmidt et al., 2015). Studies further suggest that earlier assembly states of Aβ, such as oligomers and protofibrils, may be neurotoxic in the dog’s brain (Head et al., 2010). The levels of Aβ soluble oligomers in the CSF correlated inversely with Aβ load in the CCD affected beagle brains (Head et al., 2010). Precipitates from the CSF of demented Samoyed dog with CCD acted highly neurotoxic in in vitro tests and were more neurotoxic than the synthetic oligomeric and fibrillary forms of Aβ (Rusbridge et al., 2018).