Anti-ABeta Immunity Against Alzheimer's Disease

针对阿尔茨海默病的抗 Aβ 免疫

• 批准号: 6608023
• 负责人: KENNETH EUGENE UGEN
• 金额: $ 35.69万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6608023
• 关键词: Alzheimer's disease; amyloid proteins; antigen antibody reaction; biotechnology; cellular immunity; computer data analysis; cytokine; disease /disorder prevention /control; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; helper T lymphocyte; humoral immunity; image processing; immunocytochemistry; immunologic memory; immunoregulation; laboratory mouse; leukocyte activation /transformation; neuroprotectants; polymerase chain reaction; statistics /biometry; suppressor T lymphocyte; synthetic vaccines; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a neurodegenerative disease characterized by overproduction of Abeta-amyloid from amyloid precursor protein (APP), with the subsequent pathologic deposition of Abeta into extracellular plaques in regions of the brain which are important for memory. Recently we, as well as others, have demonstrated that vaccination of a transgenic (Tg) mouse which expresses mutant presenilin-1 and APP (and serves as a model for AD) with an Abeta(1-42) peptide, resulted in amelioration of neural pathology and protection of these mice from functional memory deficits. Others have indicated that humoral immunity plays a major role in at least ameliorating the neural pathology. However, the exact role of cellular immunity, whether beneficial or deleterious, has not been addressed. We have recently demonstrated that vaccination of Tg mice with Abeta results in the induction of antibodies indicative of a T helper 2 response. We have also shown strong T cell proliferative activity in mice vaccinated with Abeta stimulated with specific antigen. A chimeric mouse line has recently been developed which expresses human MHC I and II molecules and is called CHAD (chimeric human A2DR). We propose to use this mouse to cross mate with the doubly transgenic mice described above to ask important questions about human immune responses to Abeta. The specific aims of this proposal are as follows: (a) evaluation of the CD4 T cell responses to Abeta in a Tg mouse model for AD; (b) evaluation of the potential role of CD4 T cell responses after Abeta vaccination; (c) evaluation of the CD8 T cell responses in Tg mouse models; and (d) engineering of specific immune responses in AD Tg mice. These studies will comprehensively address the potential role of cellular immune responses to Abeta vaccines.

描述（由申请人提供）：阿尔茨海默氏病（AD）是 神经退行性疾病的特征是阿比淀粉样蛋白过量生产 从淀粉样蛋白前体蛋白（APP），随后的病理 将Abeta沉积到大脑区域的细胞外斑块中 对于记忆很重要。最近，我们和其他人都证明了 表达突变体的转基因（TG）小鼠的疫苗接种 Presenilin-1和App（并用ABETA作为AD的模型）（1-42） 肽，导致神经病理的改善和保护 功能记忆缺陷的小鼠。其他人表明 免疫力在至少改善神经病理学方面起着重要作用。 但是，细胞免疫的确切作用，无论是有益还是 有害，尚未得到解决。我们最近证明了 用ABETA的TG小鼠的疫苗接种导致抗体诱导 表示T辅助2响应。我们还显示出强大的T细胞 用特异性刺激的ABETA接种的小鼠中的增生活性 抗原。最近已经开发了一条嵌合小鼠系 人MHC I和II分子，称为乍得（嵌合人A2DR）。我们 建议使用此鼠标与双重转基因小鼠交叉 上面描述的是询问有关人类免疫反应的重要问题 Abeta。该提案的具体目的如下：（a）评估 在AD的TG小鼠模型中，CD4 T细胞对ABETA的响应； （b）评估 Abeta疫苗接种后CD4 T细胞反应的潜在作用； （c）评估TG小鼠模型中CD8 T细胞响应；和 （d）AD TG小鼠特异性免疫反应的工程。这些研究会 全面解决细胞免疫反应的潜在作用 Abeta疫苗。