ANIMAL MODEL OF ALZHEIMER'S DISEASE

本提案的目的是将犬作为动物模型进行检查 老年痴呆症（AD） 一些调查人员已经表明， 阿尔茨海默病样神经病理学（ADLN）发生在老年犬中。（1-10） 据报道，狗有类胶质斑块，（1，5，6，7）老年性 淀粉样斑块（2，3，9）和神经纤维缠结。（2，4）初步 在这项工作中，我们的实验室已经检查了小猎犬的大脑， 在一个环境受控的实验室群体中长大， 他们大脑中斑块的分布与 人AD（6）。 所研究的动物没有接受任何实验性治疗。 治疗后，58%的人发现他们的大脑中有斑块形成。 此外，狗的窝与狗的窝之间有明显的关系， 出生于老年，老年时大脑中出现斑块。（六） 因此，还发现具有斑块的同窝动物具有 斑块，而那些没有斑块的同窝仔没有斑块。 的 同窝仔和牙菌斑形成的关联表明， 斑块的形成可能是由于一些产前影响，并可能是 遗传的 遗传假说与人类的数据是一致的， 常染色体显性遗传，年龄依赖性， 家族性AD患者的亲属。(11)该提案基于 这些初步发现将更全面地定义犬的病理学。 的 重点是检查作为ADLN动物模型的狗。 更 具体而言：1）我们将调整人类和啮齿动物的神经行为测试， 记忆和感觉功能的建立程度 犬痴呆与ADLN的存在之间的关系。2)我们将 研究了患有先天性心脏病的狗的父母和后代的大脑， 遗传史，以确定斑块的发生是否 基因影响。3)我们将检查各种各样的大脑， 狗的品种，以确定哪些品种有最高的发病率， ADLN。

The objective of this proposal is to examine the dog as an animal model of Alzheimer's disease (AD). Several investigators have shown that Alzheimer's disease like neuropathology (ADLN) occurs in aged dogs.(1-10) Dogs have been reported to have preamyloid plaques, (1,5,6,7) senile amyloid plaques (2,3,9) and neurofibrillary tangles. (2,4) In preliminary work, our laboratory has examined the brains of beagle dogs which were raised in an environmentally controlled laboratory colony and found that the distribution of plaques in their brains was similar to that found in human AD(6). The animals studied did not receive any experimental treatment, and 58% were found to have plaque formations in their brains. Additionally, there is an apparent relationship between the litter a dog was born in and the occurrence of plaques in its brain at old age.(6) Thus, animals who had littermates with plaques were also found to have plaques, and those without plaques had littermates without plaques. The association of littermates and plaque formation suggests that canine plaque formation may be due to some prenatal influence, and may be genetic. The genetic hypothesis would be consistent with human data of autosomal dominant inheritance with age-dependent penetrance among relatives of patients with familial AD. (11) This proposal builds on these initial findings and will define the dog pathology more fully. The focus is on the examination of the dog as an animal model of ADLN. More specifically: 1) We will adapt human and rodent neurobehavioral tests of memory and sensory function to the dog to establish the degree of relationship between canine dementia and the presence of ADLN. 2) We will examine the brains from parents and offspring of dogs with established genetic histories to determine if the occurrence of plaques is genetically influenced. 3) We will examine brains from a variety of breeds of dogs to determine which breeds have the highest incidence of ADLN.