Habiba Umma, Ozawa Makiko, Chambers James K, Uchida Kazuyuki, Descallar Joseph, Nakayama Hiroyuki, Summers Brian A, Morley John W, Tayebi Mourad
School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
Department of Veterinary Pathology, the University of Tokyo, Japan.
J Alzheimers Dis Rep. 2021 Oct 6;5(1):749-760. doi: 10.3233/ADR-210035. eCollection 2021.
Canine cognitive dysfunction (CCD) is a progressive syndrome recognized in mature to aged dogs with a variety of neuropathological changes similar to human Alzheimer's disease (AD), for which it is thought to be a good natural model. However, the presence of hyperphosphorylated tau protein (p-Tau) in dogs with CCD has only been demonstrated infrequently.
The aim of the present study was to investigate the presence of p-Tau and amyloid-β oligomer (Aβo) in cerebral cortex and hippocampus of dogs with CCD, with focus on an epitope retrieval protocol to unmask p-Tau.
Immunohistochemical and immunofluorescence analysis of the cortical and hippocampal regions of five CCD-affected and two nondemented aged dogs using 4G8 anti-Aβp, anti-Aβ nanobody (PrioAD13) and AT8 anti-p-Tau (Ser202, Thr205) antibody were used to demonstrate the presence of Aβ plaques (Aβp) and Aβ oligomers and p-Tau deposits, respectively.
The extracellular Aβ senile plaques were of the diffuse type which lack the dense core normally seen in human AD. While p-Tau deposits displayed a widespread pattern and closely resembled the typical human neuropathology, they did not co-localize with the Aβp. Of considerable interest, however, widespread intraneuronal deposition of Aβ oligomers were exhibited in the frontal cortex and hippocampal region that co-localized with p-Tau.
Taken together, these findings reveal further shared neuropathologic features of AD and CCD, supporting the case that aged dogs afflicted with CCD offer a relevant model for investigating human AD.
犬认知功能障碍（CCD）是一种在成熟至老年犬中出现的进行性综合征，具有多种与人类阿尔茨海默病（AD）相似的神经病理学变化，因此被认为是一种良好的自然模型。然而，仅偶尔在患有CCD的犬中证实过高磷酸化tau蛋白（p-Tau）的存在。
本研究旨在调查患有CCD的犬大脑皮质和海马中p-Tau和淀粉样β寡聚体（Aβo）的存在情况，重点是采用抗原修复方案来揭示p-Tau。
使用4G8抗Aβp、抗Aβ纳米抗体（PrioAD13）和AT8抗p-Tau（Ser202，Thr205）抗体，对五只患有CCD的犬和两只无痴呆的老年犬的皮质和海马区域进行免疫组织化学和免疫荧光分析，分别以证明Aβ斑块（Aβp）、Aβ寡聚体和p-Tau沉积物的存在。
细胞外Aβ老年斑为弥漫型，缺乏人类AD中常见的致密核心。虽然p-Tau沉积物呈广泛分布模式，与典型的人类神经病理学非常相似，但它们与Aβp并不共定位。然而，相当有趣的是，额叶皮质和海马区域出现了广泛的神经元内Aβ寡聚体沉积，且与p-Tau共定位。
综上所述，这些发现揭示了AD和CCD进一步的共同神经病理学特征，支持了患有CCD的老年犬可作为研究人类AD相关模型的观点。
