Besides Aβ plaques, recruitment and activation of astrocytes and microglial cells has been noticed in dogs with CCD (astrocytosis, microgliosis) (Smolek et al., 2016; Rusbridge et al., 2018) along with astrocyte hypertrophy (Borràs et al., 1999). Furthermore, the levels of pathological Aβ in the canine prefrontal cortex were positively correlated with age but neither with the severity of cognitive deficits (Gómez-Pinedo et al., 2016) nor the neuronal cell loss (Cummings et al., 1993). Neprilysin (NEP) mRNA, coding for a pivotal Aβ-degrading protein, was poorly expressed in the prefrontal cortex of aged dogs with CCD (Canudas et al., 2014), similar to human AD brain, where areas with higher Aβ aggregation express lower levels of NEP (Reilly, 2001).