Sarasa Manuel, Pesini Pedro
Araclon Biotech S.L., 50004 Zaragoza, Spain.
Curr Alzheimer Res. 2009 Apr;6(2):171-8. doi: 10.2174/156720509787602834.
The most common animal models currently used for Alzheimer disease (AD) research are transgenic mice that express a mutant form of human Abeta precursor protein (APP) and/or some of the enzymes implicated in their metabolic processing. However, these transgenic mice carry their own APP and APP-processing enzymes, which may interfere in the production of different amyloid-beta (Abeta) peptides encoded by the human transgenes. Additionally, the genetic backgrounds of the different transgenic mice are a possible confounding factor with regard to crucial aspects of AD that they may (or may not) reproduce. Thus, although the usefulness of transgenic mice is undisputed, we hypothesized that additional relevant information on the physiopathology of AD could be obtained from other natural non-transgenic models. We have analyzed the chick embryo and the dog, which may be better experimental models because their enzymatic machinery for processing APP is almost identical to that of humans. The chick embryo is extremely easy to access and manipulate. It could be an advantageous natural model in which to study the cell biology and developmental function of APP and a potential assay system for drugs that regulate APP processing. The dog suffers from an age-related syndrome of cognitive dysfunction that naturally reproduces key aspects of AD including Abeta cortical pathology, neuronal degeneration and learning and memory disabilities. However, dense core neuritic plaques and neurofibrillary tangles have not been consistently demonstrated in the dog. Thus, these species may be natural models with which to study the biology of AD, and could also serve as assay systems for Abeta-targeted drugs or new therapeutic strategies against this devastating disease.
目前用于阿尔茨海默病（AD）研究的最常见动物模型是转基因小鼠，它们表达人类β淀粉样前体蛋白（APP）的突变形式和/或一些参与其代谢加工的酶。然而，这些转基因小鼠携带自身的APP和APP加工酶，这可能会干扰人类转基因所编码的不同β淀粉样肽（Aβ）的产生。此外，不同转基因小鼠的遗传背景对于它们可能（或可能不）重现的AD关键方面而言是一个潜在的混杂因素。因此，尽管转基因小鼠的实用性无可争议，但我们推测可以从其他天然非转基因模型中获得有关AD生理病理学的更多相关信息。我们分析了鸡胚和狗，它们可能是更好的实验模型，因为它们加工APP的酶机制与人类几乎相同。鸡胚极易获取和操作。它可能是研究APP细胞生物学和发育功能的有利天然模型，也是用于调节APP加工的药物的潜在检测系统。狗患有与年龄相关的认知功能障碍综合征，自然地重现了AD的关键方面，包括Aβ皮质病理学、神经元变性以及学习和记忆障碍。然而，致密核心神经炎性斑块和神经原纤维缠结在狗身上尚未得到一致证实。因此，这些物种可能是用于研究AD生物学的天然模型，也可作为针对Aβ的药物或针对这种毁灭性疾病的新治疗策略的检测系统。
