title: The domestic cat as a natural animal model of Alzheimer's disease.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: James K
authors.initials: JK
authors.lastname: Chambers
authors.affiliation: Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. auchidak@mail.ecc.u-tokyo.ac.jp.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Ishii
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Harutsugu
authors.initials: H
authors.lastname: Tatebe
authors.affiliation: Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Department of Neuroscience, Osaka City University Graduate School of Medicine, Osaka, Japan. tomi@med.osaka-cu.ac.jp.
authors.forename: Takami
authors.initials: T
authors.lastname: Tomiyama
authors.affiliation: Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Une
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002415:Cats; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D016875:tau Proteins