ANIMAL MODEL OF ALZHEIMER'S DISEASE

这项建议的目的是将狗作为动物模型进行检验。 阿尔茨海默病(AD)。几名调查人员已经证明， 阿尔茨海默病样神经病理(ADLN)发生在老年狗身上。 据报道，狗有(1，5，6，7)老年性前叶样斑块 淀粉样斑块(2，3，9)和神经原纤维缠结。(2，4)初赛 在工作中，我们的实验室检查了比格犬的大脑，这些狗 在一个受环境控制的实验室群体中长大，发现 他们大脑中的斑块分布与在 人AD(6)。被研究的动物没有接受任何实验 治疗后，58%的人被发现大脑中有斑块形成。 此外，一窝狗和一只狗之间存在着明显的关系 出生于晚年，大脑中出现斑块。 因此，那些产下有斑块的产仔的动物也被发现患有 斑块，无斑块的产仔数无斑块。这个 产仔数和斑块形成的关系表明，犬类 斑块的形成可能是由于一些产前的影响，也可能是 遗传的。基因假说将与人类数据相一致 常染色体显性遗传与年龄相关的外显性 家族性阿尔茨海默病患者亲属。(11)这项建议的基础是 这些初步发现将更全面地定义狗的病理学。这个 重点是将狗作为ADLN的动物模型进行检查。更多 具体地说：1)我们将采用人类和啮齿动物的神经行为测试 对狗的记忆和感觉功能的建立程度 犬痴呆与ADLN存在的关系2)我们会 检查已确诊的狗的父母和后代的大脑 遗传史来确定斑块的发生是否 受基因影响。3)我们将检查来自不同国家的大脑 以确定哪些品种的狗的发病率最高 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.