The domestic cat as a natural animal model of Alzheimer’s disease

Abstract

IntroductionAlzheimer’s disease (AD) is the most dominant neurodegenerative disorder that causes dementia, and no effective treatments are available. To study its pathogenesis and develop therapeutics, animal models representing its pathologies are needed. Although many animal species develop senile plaques (SP) composed of amyloid-β (Aβ) proteins that are identical to those found in humans, none of them exhibit neurofibrillary tangles (NFT) and subsequent neurodegeneration, which are integral parts of the pathology of AD.ResultsThe present study shows that Aβ accumulation, NFT formation, and significant neuronal loss all emerge naturally in the hippocampi of aged domestic cats. The NFT that form in the cat brain are identical to those seen in human AD in terms of their spatial distribution, the cells they affect, and the tau isoforms that comprise them. Interestingly, aged cats do not develop mature argyrophilic SP, but instead accumulate intraneuronal Aβ oligomers in their hippocampal pyramidal cells, which might be due to the amino acid sequence of felid Aβ.ConclusionsThese results suggest that Aβ oligomers are more important than SP for NFT formation and the subsequent neurodegeneration. The domestic cat is a unique animal species that naturally replicates various AD pathologies, especially Aβ oligomer accumulation, NFT formation, and neuronal loss.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0258-3) contains supplementary material, which is available to authorized users.

A 4R tauopathy develops without amyloid deposits in aged cat brains

“…Many mammals, including wild-type mice, do not develop spontaneously NFTs during aging, but the development of a tau pathology is not specific to human species. Abnormal tau phosphorylation is also described in other aged mammals (Hartig et al, 2000;Youssef et al, 2016), such as cats (Chambers et al, 2015;Gunn-Moore et al, 2006;Head et al, 2005), dogs (Papaioannou et al, 2001;Yu et al, 2011), sheep (Braak et al, 1994a;Nelson et al, 1994;Reid et al, 2017), octogon degu (van Groen et al, 2011), brown bears (Cork et al, 1988), lemurian Microcebus (Bons et al, 1995), and cynomolgus monkeys (Oikawa et al, 2010;Uchihara et al, 2016), in the presence (Chambers et al, 2015;Cork et al, 1988;Gunn-Moore et al, 2006;Head et al, 2005;Oikawa et al, 2010;Papaioannou et al, 2001;Reid et al, 2017;Uchihara et al, 2016;van Groen et al, 2011;Yu et al, 2011), as well as in the absence (Braak et al, 1994a;Nelson et al, 1994), of Ab deposits. In cats, a previous study concluded that phosphorylated tau proteins, composed of both 3R and 4R isoforms, formed aggregates only in the presence of amyloid (Chambers et al, 2015).…”

The Exceptional Vulnerability of Humans to Alzheimer’s Disease

“…Identical paired helical filaments have been described in an older chimpanzee (discussed above), but not yet in any other primate species. Naturally occurring tauopathies have also been reported in several nonprimate species, including bears [85], cats [86], goats, and cattle [87, 88], but these conditions do not resemble AD pathologically.…”

Cross species application of quantitative neuropathology assays developed for clinical Alzheimer’s disease samples

“…Similarly, some studies report AT8reactive pTau in aged vervets [12], others detected either no or different pTau epitopes in rhesus monkeys or marmosets [18,19]. It will be of interest to apply our current investigation not only to larger samples, but also to additional species, for example cats [20], that could be used as novel alternative models for the study of AD neuropathologic change.…”