ANIMAL MODEL OF ALZHEIMER'S DISEASE

阿尔茨海默病动物模型

• 批准号: 3123296
• 负责人: MICHAEL J RUSSELL
• 金额: $ 14.6万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3123296
• 关键词: Alzheimer's disease; animal population genetics; animal tissue; disease /disorder model; dogs; electroencephalography; ethology; histopathology; immunocytochemistry; memory; model design /development; neuritic plaques; neuropsychological tests; olfactory threshold; sensory discrimination; species difference; tissue resource /registry

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.

该提案的目的是将狗作为动物模型进行检查 阿尔茨海默病（AD）。 几位研究人员表明 老年犬会出现类似阿尔茨海默病的神经病理学 (ADLN)。(1-10) 据报道，狗有前淀粉样斑块，(1,5,6,7)老年 淀粉样蛋白斑 (2,3,9) 和神经原纤维缠结。 (2,4) 初步 在工作中，我们的实验室检查了比格犬的大脑 在环境受控的实验室群体中饲养并发现 他们大脑中斑块的分布与在 人类AD(6)。 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，狗的一窝幼崽之间也存在明显的关系。 出生时大脑中出现斑块，老年时出现斑块。(6) 因此，同窝出生的动物也发现有斑块 斑块，而那些没有斑块的孩子则有没有斑块的同窝仔猪。 这 同窝出生的动物和斑块形成的关联表明犬 斑块的形成可能是由于某些产前影响，并且可能是 遗传。 遗传假说与人类数据一致 常染色体显性遗传，外显率与年龄有关 家族性 AD 患者的亲属。 (11) 本提案建立在 这些初步发现将更全面地定义狗的病理学。 这 重点是对作为 ADLN 动物模型的狗进行检查。 更多的 具体来说： 1）我们将调整人类和啮齿动物的神经行为测试 给狗建立记忆和感觉功能的程度 犬痴呆与 ADLN 之间的关系。 2）我们会 检查狗的父母和后代的大脑 遗传史以确定斑块的发生是否是 受遗传影响。 3）我们将检查不同部位的大脑 狗的品种，以确定哪些品种的发病率最高 ADLN。