Alzheimer’s disease (AD) is a significant burden for human health that is increasing in prevalence as the global population ages. There is growing recognition that current preclinical models of AD are insufficient to recapitulate key aspects of the disease. Laboratory models for AD include mice, which do not naturally develop AD-like pathology during aging, and laboratory Beagle dogs, which do not share the human environment. In contrast, the companion dog shares the human environment and presents a genetically heterogeneous population of animals that might spontaneously develop age-associated AD-like pathology and cognitive dysfunction. Here, we quantitatively measured amyloid beta (Aβ42 or Abeta-42) levels in three areas of the companion dog brain (prefrontal cortex, temporal cortex, hippocampus/entorhinal cortex) and cerebrospinal fluid (CSF) using a newly developed Luminex assay. We found significant positive correlations between Aβ42 and age in all three brain regions. Brain Aβ42 abundance in all three brain regions was also correlated with Canine Cognitive Dysfunction Scale score in a multivariate analysis. This latter effect remained significant when correcting for age, except in the temporal cortex. There was no correlation between Aβ42 in CSF and cognitive scores; however, we found a significant positive correlation between Aβ42 in CSF and body weight, as well as a significant negative correlation between Aβ42 in CSF and age. Our results support the suitability of the companion dog as a model for AD and illustrate the utility of veterinary biobanking to make biospecimens available to researchers for analysis.

阿尔茨海默病 (AD) 是人类健康的一个重大负担，随着全球人口老龄化，其患病率正在增加。人们越来越认识到，目前的 AD 临床前模型不足以概括该疾病的关键方面。AD 的实验室模型包括在衰老过程中不会自然发展出 AD 样病理的小鼠，以及不共享人类环境的实验室 Beagle 犬。相比之下，伴侣犬共享人类环境，并呈现出基因异质的动物种群，这些动物可能会自发地发展出与年龄相关的 AD 样病理和认知功能障碍。在这里，我们定量测量了伴侣犬大脑三个区域（前额叶皮层、颞叶皮层、海马/内嗅皮质）和脑脊液（CSF）使用新开发的 Luminex 检测。我们发现所有三个大脑区域的 Aβ42 与年龄之间存在显着的正相关。在多变量分析中，所有三个脑区的脑 Aβ42 丰度也与犬认知功能障碍量表评分相关。在校正年龄时，后一种效应仍然很显着，除了颞叶皮层。脑脊液中的 Aβ42 与认知评分之间没有相关性；然而，我们发现脑脊液中的 Aβ42 与体重之间存在显着的正相关，而脑脊液中的 Aβ42 与年龄之间存在显着的负相关。我们的结果支持伴侣犬作为 AD 模型的适用性，并说明了兽医生物库的实用性，可以使研究人员可以使用生物样本进行分析。