Prevention approaches in a preclinical canine model of Alzheimer's disease: benefits and challenges.
Prevention approaches in a preclinical canine model of Alzheimer's disease: benefits and challenges.
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DOI：
10.3389/fphar.2014.00047
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发表时间：
2014
影响因子：
5.6
通讯作者：
Head E
中科院分区：
文献类型：
--
作者：
Davis PR;Head E
老年狗会自发地发展出许多人类衰老和阿尔茨海默病(AD)的特征，包括认知能力下降和神经病理。在这篇综述中，我们讨论了与年龄相关的学习任务、记忆任务以及可用于老年犬敏感治疗结果测量的功能测量。描述了与认知下降有关的神经病理学，以及治疗研究的例子，这些研究表明老年狗的神经病理减少(饮食操作、行为丰富、免疫治疗和他汀类药物)。在犬身上的研究表明，多靶点方法可能比单途径操作(例如，结合抗氧化剂和行为丰富)更有益。老龄犬的研究表明，对人类临床试验结果的良好预测有效性(例如，免疫疗法)，以及在狗身上测试的几种干预措施强烈支持预防方法(例如，免疫疗法和他汀类药物)。此外，狗非常适合于预防研究，因为它们的年龄较大，因为认知衰退和神经病理的开始有力地支持了可以在3-5年内完成的纵向干预。使用犬科动物模型的缺点是它们耗时长，使用劳动密集型综合认知测试，并且涉及昂贵的住房(几乎与非人类灵长类动物一样高)。然而，总体而言，将狗作为测试AD预防方法的临床前模型可能会补充啮齿动物和非人类灵长类动物的工作。
Aged dogs spontaneously develop many features of human aging and Alzheimer’s disease (AD) including cognitive decline and neuropathology. In this review, we discuss age-dependent learning tasks, memory tasks, and functional measures that can be used in aged dogs for sensitive treatment outcome measures. Neuropathology that is linked to cognitive decline is described along with examples of treatment studies that show reduced neuropathology in aging dogs (dietary manipulations, behavioral enrichment, immunotherapy, and statins). Studies in canine show that multi-targeted approaches may be more beneficial than single pathway manipulations (e.g., antioxidants combined with behavioral enrichment). Aging canine studies show good predictive validity for human clinical trials outcomes (e.g., immunotherapy) and several interventions tested in dogs strongly support a prevention approach (e.g., immunotherapy and statins). Further, dogs are ideally suited for prevention studies as they the age because onset of cognitive decline and neuropathology strongly support longitudinal interventions that can be completed within a 3–5 year period. Disadvantages to using the canine model are that they lengthy, use labor-intensive comprehensive cognitive testing, and involve costly housing (almost as high as that of non-human primates). However, overall, using the dog as a preclinical model for testing preventive approaches for AD may complement work in rodents and non-human primates.
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影响因子：
4.2
作者：
Colle, MA;Hauw, JJ;Duykaerts, C
通讯作者：
Duykaerts, C
影响因子：
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影响因子：
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通讯作者：
Lindblad-Toh, Kerstin
影响因子：
12.7
作者：
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通讯作者：
Lintner, F