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.
Highlights
Alzheimer’s disease (AD) is the most dominant neurodegenerative disorder that causes dementia, and no effective treatments are available
These parenchymal Aβ deposits in cat brains had no central core as seen in mature plaques of human AD and Tg mouse models of AD, and were not visualized by silver staining or Congo red staining
Neither of the bands corresponding to Aβ hexamers or dodecamers was detected with anti-ApoE antibody, indicating that these oligomers are not bound with ApoE (Additional file 1: Figure S2b)
Summary
Alzheimer’s disease (AD) is the most dominant neurodegenerative disorder that causes dementia, and no effective treatments are available. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by three major pathologies: senile plaques (SPs), neurofibrillary tangles (NFTs), and neuronal loss. The former two are extracellular and intracellular argyrophilic aggregates composed of amyloid β (Aβ) and hyperphosphorylated tau protein, respectively. Accumulating evidence indicates that Aβ accumulation leads to NFT formation and subsequent neuronal loss and cognitive dysfunction [24, 29, 47] Based on this notion, various transgenic (Tg) mouse models have been generated by introducing human APP (amyloid precursor protein) or PSEN (presenilin) with the mutations linked to familial AD [23].
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