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Acta Neuropathol Commun. 2015 Dec 10;3:78. doi: 10.1186/s40478-015-0258-3.

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

Author information

1
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
2
Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan.
3
Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
4
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. auchidak@mail.ecc.u-tokyo.ac.jp.
5
Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
6
Department of Neuroscience, Osaka City University Graduate School of Medicine, Osaka, Japan. tomi@med.osaka-cu.ac.jp.

Abstract

INTRODUCTION:

Alzheimer'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.

RESULTS:

The 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.

CONCLUSIONS:

These 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.

PMID:
26651821
PMCID:
PMC4674944
DOI:
10.1186/s40478-015-0258-3
[Indexed for MEDLINE]
Free PMC Article

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