The Domestic Cat As a Natural Animal Model of Alzheimer's Disease

Overview

Journal Acta Neuropathol Commun

Publisher Biomed Central

Specialty Neurology

Date 2015 Dec 15

PMID 26651821

Citations 43

Authors

James K Chambers

Takahiko Tokuda

Kazuyuki Uchida

Ryotaro Ishii

Harutsugu Tatebe

Erika Takahashi

Takami Tomiyama

Yumi Une

Hiroyuki Nakayama

Affiliations

Soon will be listed here.

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.

Citing Articles

Amyloid-Beta, Tau, and Microglial Activation in Aged Felid Brains.

Kulik V, Edler M, Raghanti M, Imam A, Sherwood C J Comp Neurol. 2024; 532(11):e25679.

PMID: 39474737 PMC: 11572721. DOI: 10.1002/cne.25679.

Challenges and future directions of SUDEP models.

Gu J, Shao W, Liu L, Wang Y, Yang Y, Zhang Z Lab Anim (NY). 2024; 53(9):226-243.

PMID: 39187733 DOI: 10.1038/s41684-024-01426-y.

Resilience to aging drives personalized intervention strategies for Alzheimer's disease.

Wezeman J, Keely A, Ladiges W Aging Pathobiol Ther. 2024; 5(4):151-153.

PMID: 39104382 PMC: 11299896. DOI: 10.31491/apt.2023.12.127.

Stress and the domestic cat: have humans accidentally created an animal mimic of neurodegeneration?.

Niesman I Front Neurol. 2024; 15:1429184.

PMID: 39099784 PMC: 11294998. DOI: 10.3389/fneur.2024.1429184.

Treatment with 1, 10 Phenanthroline-5-Amine Reduced Amyloid Burden in a Mouse Model of Alzheimer's Disease.

Schmued L, Maloney B, Schmued C, Lahiri D J Alzheimers Dis. 2023; 97(1):239-247.

PMID: 38073385 PMC: 10789349. DOI: 10.3233/JAD-221285.

References

Chambers J, Uchida K, Harada T, Tsuboi M, Sato M, Kubo M . Neurofibrillary tangles and the deposition of a beta amyloid peptide with a novel N-terminal epitope in the brains of wild Tsushima leopard cats. PLoS One. 2012; 7(10):e46452. PMC: 3463583. DOI: 10.1371/journal.pone.0046452. View

Oddo S, Caccamo A, Smith I, Green K, LaFerla F . A dynamic relationship between intracellular and extracellular pools of Abeta. Am J Pathol. 2006; 168(1):184-94. PMC: 1592652. DOI: 10.2353/ajpath.2006.050593. View

Frank S, Clavaguera F, Tolnay M . Tauopathy models and human neuropathology: similarities and differences. Acta Neuropathol. 2007; 115(1):39-53. DOI: 10.1007/s00401-007-0291-9. View

Bernstein S, Dupuis N, Lazo N, Wyttenbach T, Condron M, Bitan G . Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. Nat Chem. 2010; 1(4):326-31. PMC: 2918915. DOI: 10.1038/nchem.247. View

Umeda T, Maekawa S, Kimura T, Takashima A, Tomiyama T, Mori H . Neurofibrillary tangle formation by introducing wild-type human tau into APP transgenic mice. Acta Neuropathol. 2014; 127(5):685-98. DOI: 10.1007/s00401-014-1259-1. View

Selkoe D . Resolving controversies on the path to Alzheimer's therapeutics. Nat Med. 2011; 17(9):1060-5. DOI: 10.1038/nm.2460. View

Uchida K, Yoshino T, Yamaguchi R, Tateyama S, Kimoto Y, Nakayama H . Senile plaques and other senile changes in the brain of an aged American black bear. Vet Pathol. 1995; 32(4):412-4. DOI: 10.1177/030098589503200410. View

Ma Q, Yang F, Rosario E, Ubeda O, Beech W, Gant D . Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci. 2009; 29(28):9078-89. PMC: 3849615. DOI: 10.1523/JNEUROSCI.1071-09.2009. View

Johnson W, Eizirik E, Pecon-Slattery J, Murphy W, Antunes A, Teeling E . The late Miocene radiation of modern Felidae: a genetic assessment. Science. 2006; 311(5757):73-7. DOI: 10.1126/science.1122277. View

10.

Hardy J, Higgins G . Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992; 256(5054):184-5. DOI: 10.1126/science.1566067. View

11.

Ittner L, Gotz J . Amyloid-β and tau--a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci. 2011; 12(2):65-72. DOI: 10.1038/nrn2967. View

12.

Saito T, Matsuba Y, Mihira N, Takano J, Nilsson P, Itohara S . Single App knock-in mouse models of Alzheimer's disease. Nat Neurosci. 2014; 17(5):661-3. DOI: 10.1038/nn.3697. View

13.

Serizawa S, Chambers J, Une Y . Beta amyloid deposition and neurofibrillary tangles spontaneously occur in the brains of captive cheetahs (Acinonyx jubatus). Vet Pathol. 2011; 49(2):304-12. DOI: 10.1177/0300985811410719. View

14.

Langui D, Girardot N, El Hachimi K, Allinquant B, Blanchard V, Pradier L . Subcellular topography of neuronal Abeta peptide in APPxPS1 transgenic mice. Am J Pathol. 2004; 165(5):1465-77. PMC: 1618656. DOI: 10.1016/s0002-9440(10)63405-0. View

15.

Gouras G, Tampellini D, Takahashi R, Capetillo-Zarate E . Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer's disease. Acta Neuropathol. 2010; 119(5):523-41. PMC: 3183823. DOI: 10.1007/s00401-010-0679-9. View

16.

Benilova I, Karran E, De Strooper B . The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci. 2012; 15(3):349-57. DOI: 10.1038/nn.3028. View

17.

Tokutake T, Kasuga K, Yajima R, Sekine Y, Tezuka T, Nishizawa M . Hyperphosphorylation of Tau induced by naturally secreted amyloid-β at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3β signaling pathway. J Biol Chem. 2012; 287(42):35222-35233. PMC: 3471719. DOI: 10.1074/jbc.M112.348300. View

18.

Duyckaerts C, Potier M, Delatour B . Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol. 2007; 115(1):5-38. PMC: 2100431. DOI: 10.1007/s00401-007-0312-8. View

19.

Capucchio M, Marquez M, Pregel P, Foradada L, Bravo M, Mattutino G . Parenchymal and vascular lesions in ageing equine brains: histological and immunohistochemical studies. J Comp Pathol. 2009; 142(1):61-73. DOI: 10.1016/j.jcpa.2009.07.007. View

20.

Fukumoto H, Tokuda T, Kasai T, Ishigami N, Hidaka H, Kondo M . High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. FASEB J. 2010; 24(8):2716-26. DOI: 10.1096/fj.09-150359. View