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Aretheus’un Tanımladığı Demans, Bugünkü Hali ile Alzheimer Hastalığının İnsan ve Köpeklerde Çift Yönlü Benzerlikleri

Year 2025, Volume: 6 Issue: 2, 102 - 115, 30.09.2025

Abstract

Alzheimer hastalığı (AH), insanlarda olduğu gibi hayvan modellerinde de karmaşık nörodejeneratif süreçlerle kendini gösterir. Hastalığın temel patolojik özellikleri arasında amiloid beta (Aβ) birikimi, tau protein hiperfosforilasyonu, sinaptik işlev bozukluğu ve bilişsel disfonksiyon yer alır. İnsan AH’sini anlamak için geliştirilen hayvan modelleri, bu patolojilerin mekanizmalarını ve hastalığın ilerleyişini incelemek için değerli araçlar sunmaktadır. Transgenik fare modelleri, genetik modifikasyonlar yoluyla Aβ birikimi ve tau protein değişikliklerini taklit ederek hastalığın moleküler ve hücresel düzeyde incelenmesini sağlar. Bu modeller, özellikle erken evre patolojik değişiklikleri ve ilaç geliştirme süreçlerini araştırmada kritik rol oynamaktadır. Doğal yaşlanma süreçlerine bağlı olarak bilişsel bozukluklar gösteren köpekler ve kediler, insan Alzheimer patolojisini daha yakından taklit eden önemli modellerdir. Özellikle yaşlı köpeklerde, beyinde Aβ plak oluşumu, sinaptik kayıplar ve nörodejenerasyon gibi değişiklikler gözlemlenir. Köpeklerin bilişsel işlevleri üzerinde yapılan davranışsal testler, insanlarda görülen öğrenme ve hafıza bozukluklarını değerlendirmek için kullanılabilir. Kedilerde de benzer nöropatolojik süreçler rapor edilmiştir, ancak bu alandaki çalışmalar daha sınırlıdır. Hayvan modelleri, insan ve hayvanlar arasında bazı fizyolojik farklılıklar bulunsa da, Alzheimer hastalığının biyolojik temellerini anlamak ve tedavi stratejileri geliştirmek için önemli bilgiler sunar. Ancak, türler arası farklılıklar göz önünde bulundurularak bu modeller dikkatle seçilmeli ve yorumlanmalıdır. Bu modeller, Alzheimer’ın karmaşık doğasını çözümlemeye katkıda bulunurken, yeni terapötik yaklaşımların geliştirilmesine yönelik klinik araştırmalara sağlam bir temel oluşturmaktadır.

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Dementia as Described by Aretheus, Its Current Form and the Bilateral Similarities of Alzheimer's Disease in Humans and Dogs

Year 2025, Volume: 6 Issue: 2, 102 - 115, 30.09.2025

Abstract

Alzheimer's disease (AD) manifests itself with complex neurodegenerative processes in animal models as well as in humans. The basic pathological features of the disease include amyloid beta (Aβ) accumulation, tau protein hyperphosphorylation, synaptic dysfunction, and cognitive dysfunction. Animal models developed to understand human AD provide valuable tools to study the mechanisms of these pathologies and the progression of the disease. Transgenic mouse models mimic Aβ accumulation and tau protein changes through genetic modifications, allowing the disease to be studied at the molecular and cellular levels. These models play a critical role in investigating early-stage pathological changes and drug development processes. Dogs and cats, which exhibit cognitive impairment due to natural aging processes, are important models that more closely mimic human AD pathology. Changes such as Aβ plaque formation, synaptic losses, and neurodegeneration are observed in the brain, especially in older dogs. Behavioral tests performed on the cognitive functions of dogs can be used to evaluate learning and memory impairments seen in humans. Similar neuropathological processes have been reported in cats, but studies in this area are more limited.
Animal models provide important information for understanding the biological basis of Alzheimer's disease and developing treatment strategies, despite some physiological differences between humans and animals. However, these models should be carefully selected and interpreted, considering species differences. These models contribute to unraveling the complex nature of Alzheimer's disease and provide a solid basis for clinical research to develop new therapeutic approaches.

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  • Bosch MN, Pugliese M, Gimeno-Bayón J, Rodriguez MJ, Mahy N. Dogs with cognitive dysfunction syndrome: a natural model of Alzheimer’s disease. Curr Alzheimer Res. 2012;9(3):298–314.
  • Fast R, Rodell A, Gjedde A, Mouridsen K, Alstrup AK, Bjarkam CR, et al. PiB fails to map amyloid deposits in cerebral cortex of aged dogs with canine cognitive dysfunction. Front Aging Neurosci. 2013;5:99.
  • Salvin HE, McGreevy PD, Sachdev PS, Valenzuela MJ. Underdiagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs. Vet J. 2010;184(3):277–281.
  • Knopman DS, Amieva H, Petersen RC, Chételat G, Holtzman DM, Hyman BT, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33.
  • Price JL, Morris JC. Tangles and plaques in nondemented aging and ‘preclinical’ Alzheimer’s disease. Ann Neurol. 1995;45(3):358–368.
  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297(5580):353–356.
  • Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, et al. Decreased clearance of CNS β-amyloid in Alzheimer’s disease. Science. 2010;330(6012):1774–1774.
  • Lin Y, Shan PY, Jiang WJ, Sheng C, Ma L. Subjective cognitive decline: preclinical manifestation of Alzheimer’s disease. Neurol Sci. 2019;40(1):41–49.
  • Gillis C, Mirzaei F, Potashman M, Ikram MA, Maserejian N. The incidence of mild cognitive impairment: a systematic review and data synthesis. Alzheimers Dement (Amst). 2019;11:248–256.
  • Chen YG. Research progress in the pathogenesis of Alzheimer’s disease. Chin Med J (Engl). 2018;131(13):1618–1624.
  • Kametani F, Hasegawa M. Reconsideration of amyloid hypothesis and tauopathy in Alzheimer's disease. Front Neurosci. 2018;12:25.
  • Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW. The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex. 1991;1(1):103–116.
  • Gómez‐Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol. 1997;41(1):17–24.
  • Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986;83(13):4913–4917.
  • Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259.
  • Insel PS, Mormino EC, Aisen PS, Thompson WK, Donohue MC. Neuroanatomical spread of amyloid β and tau in Alzheimer's disease: Implications for primary prevention. Brain Commun. 2020;2(1):fcaa007.
  • Jack CR Jr, Wiste HJ, Schwarz CG, Lowe VJ, Senjem ML, Vemuri P, et al. Longitudinal tau PET in ageing and Alzheimer’s disease. Brain. 2018;141(5):1517–1528.
  • Iqbal K, Liu F, Gong CX. Tau and neurodegenerative disease: the story so far. Nat Rev Neurol. 2016;12(1):15–27.
  • Fändrich M. Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity. J Mol Biol. 2012;421(4-5):427–440.
  • Nelson PT, Braak H, Markesbery WR. Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol. 2009;68(1):1–14.
  • Swanson KS, Vester BM, Apanavicius CJ, Kirby NA, Schook LB. Implications of age and diet on canine cerebral cortex transcription. Neurobiol Aging. 2009;30(8):1314–1326.
  • Branton W, Johnson A, Evans T. Microbial infiltration into the human brain and its implications. J Infect Dis. 2013;208(4):651–659.
  • Weber C, Dilthey A, Finzer P. The role of microbiome-host interactions in the development of Alzheimer's disease. Front Cell Infect Microbiol. 2023;13:1151021.
  • Tabatabaee M. Microbiome-Glia Crosstalk: Bridging the communication divide in the central nervous system. Neuroglia. 2024;5(2):89–104.
  • Lotz SK, Blackhurst BM, Reagin KL, Funk KE. Microbial infections are a risk factor for neurodegenerative diseases. Front Cell Neurosci. 2021;15:691136.
  • Ma Y, Sannino D, Linden JR, Haigh S, Zhao B, Grigg JB, et al. Epsilon toxin–producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege. J Clin Invest. 2023;133(9).
  • Pisa D, Alonso R, Rábano A, Rodal I, Carrasco L. Different brain regions are infected with fungi in Alzheimer’s disease. Sci Rep. 2015;5:15015.
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There are 89 citations in total.

Details

Primary Language Turkish
Subjects Veterinary Sciences (Other)
Journal Section Reviews
Authors

Hasan Erdoğan 0000-0001-5141-5108

Tahsin Barış Değer 0000-0002-4231-0782

Songül Erdoğan 0000-0002-7833-5519

Serdar Paşa 0000-0003-4957-9263

Cansu Balıkçı 0000-0002-6261-162X

İlayda Tendar 0009-0005-9303-1336

Ayşe İdil Kizilkanat 0009-0001-4185-3224

Pelin Dinç 0009-0003-6296-3304

Kerem Ural 0000-0003-1867-7143

Publication Date September 30, 2025
Submission Date December 26, 2024
Acceptance Date August 26, 2025
Published in Issue Year 2025 Volume: 6 Issue: 2

Cite

Vancouver Erdoğan H, Değer TB, Erdoğan S, Paşa S, Balıkçı C, Tendar İ, et al. Aretheus’un Tanımladığı Demans, Bugünkü Hali ile Alzheimer Hastalığının İnsan ve Köpeklerde Çift Yönlü Benzerlikleri. CPHS. 2025;6(2):102-15.