In comparison to transgenic mouse models, natural animal models better represent the pathophysiology of AD. Models of “physiologically” aged rats, degus and dogs are useful for studying mechanistic aspects of AD, which are also very valuable in the development of therapeutics that would alleviate age-related declines in cognitive function. Mouse models for AD research carry mutations, found in familial AD, and are artificially accumulating Aβ plaques and NFTs. Whether mice are good models have been thoroughly discussed elsewhere (Götz et al., 2018). Several drugs have cleared the amyloid load in mice but failed to do so in people with AD. Recently the genetic background and environmental factors have been demonstrated as the variability in AD development, which was partially recognized by incorporating genetic diversity into mouse models of AD (Neuner et al., 2018). Transgenic minipigs expressing APP695 or PSEN1 have also been developed but have not shown the histopathological nor the cognitive impairment signs (Holm et al., 2016). Therefore, natural animal models of species with spontaneously occurring neurodegeneration are potentially more useful in developing and testing novel treatments for such diseases.