CHLAMYDIA PNEUMONIAE--A PATHOGEN IN ALZHEIMERS DISEASE

肺炎衣原体——阿尔茨海默病的病原体

• 批准号: 6511143
• 负责人: ALAN PAUL HUDSON
• 金额: $ 29.1万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511143
• 关键词: Alzheimer's disease; Chlamydiaceae; clinical research; cytokine; disease /disorder etiology; disease /disorder onset; electron microscopy; glia; human subject; immunocytochemistry; microglia; molecular pathology; neuropathology; polymerase chain reaction; tissue /cell culture

DESCRIPTION (Adapted from the Applicant's Abstract): Late-onset Alzheimer's disease (AD) afflicts millions of individuals and is thought to be the most important single cause of senile dementia. This disease has no clearly defined etiology at the present time, and the detailed events that initiate and maintain the pathogenic process ending in the disease remain to be elucidated. However, one risk factor for development of late-onset AD has been identified: possession of the APOE E4 allele. The investigators demonstrated that the obligate intracellular bacterial parasite Chlamydia pneumoniae is associated with late-onset AD. That is, they showed that autopsy tissues from affected brain regions of AD patients are PCR-positive for the organism in 90% of samples examined, whereas virtually no congruent tissues from control brains, or tissues from unaffected brain areas of AD patients, were similarly positive. Extensive electron microscopic, immunoelectron microscopic and immunohistochemical study of AD and control brains allowed visualization of the organism in these samples, definition of host cells as microglia and astroglia, and provided clear evidence that chlamydia-infected cells are located almost exclusively in brain regions showing AD related neuropathology. Importantly, in more recent studies they demonstrated that the APOE E4 allele or its gene product is actually associated with increased pathobiology of C pneumoniae. In the present application, they describe studies to extend these provocative initial observations. They will extend their initial studies of the presence and location of C. pneumoniae in the AD brain in another, larger, and more clinically well defined set of AD and control tissues. They will determine whether similar chlamydial infection obtains in other neurodegenerative diseases, and they will define the relationship between C. pneumoniae infected cells/cell types to neuropathology. Further, they will define the contribution of C. pneumoniae to the production of inflammatory mediators known to be associated with AD pathology, and they will determine whether C. pneumoniae-infected astroglia and microglia contribute to production and deposition of aberrant amyloid and PHF-tau in the AD brain. The research proposed in this application will confirm that C pneumoniae infection of the brain is specific to patients with late-onset AD and define molecular mechanisms by which the organism promotes/exacerbates the disease. Such new information may well provide important new insights for development of novel therapeutic modalities to prevent or ameliorate late-onset AD.

描述（改编自申请人的摘要）：迟发性阿尔茨海默病 疾病（AD）困扰着数百万人，被认为是最严重的疾病 老年性痴呆的重要单一原因。这种病没有明确的定义 目前的病因学，以及引发和发生的详细事件 维持疾病的致病过程仍有待阐明。 然而，已确定发生迟发性 AD 的一个危险因素： 拥有 APOE E4 等位基因。调查人员证明， 专性细胞内细菌寄生虫肺炎衣原体相关 患有迟发性 AD。也就是说，他们表明，来自受影响的尸检组织 AD 患者的大脑区域中 90% 的生物体 PCR 呈阳性 检查样本，而对照大脑中几乎没有一致的组织， 或来自 AD 患者未受影响的大脑区域的组织也呈类似阳性。 广泛的电子显微镜、免疫电子显微镜和 AD 和对照大脑的免疫组织化学研究允许可视化 这些样本中的有机体，将宿主细胞定义为小胶质细胞和星形胶质细胞， 并提供了明确的证据表明衣原体感染的细胞几乎位于 仅在显示 AD 相关神经病理学的大脑区域中。重要的是，在 最近的研究表明，APOE E4 等位基因或其基因 该产品实际上与肺炎衣原体病理学的增加有关。在 在本申请中，他们描述了扩展这些挑衅性的研究 初步观察。他们将扩展对存在的初步研究 肺炎衣原体在 AD 大脑中的位置在另一个更大的地方 临床上明确定义的一组 AD 和对照组织。他们将确定 类似的衣原体感染是否也出现在其他神经退行性疾病中 疾病，并且他们将定义肺炎衣原体感染之间的关系 细胞/细胞类型到神经病理学。此外，他们将定义贡献 肺炎衣原体产生已知的炎症介质 与 AD 病理相关，他们将确定 C. 肺炎链球菌感染的星形胶质细胞和小胶质细胞有助于生产和 AD 大脑中异常淀粉样蛋白和 PHF-tau 的沉积。研究 本申请中提出的将确认肺炎衣原体感染 大脑是迟发性 AD 患者特有的，并定义分子 生物体促进/加剧疾病的机制。这么新的 信息很可能为小说的发展提供重要的新见解 预防或改善迟发性 AD 的治疗方式。

项目成果

Role of infection in Alzheimer's disease.

感染在阿尔茨海默病中的作用。

• 发表时间: 2001
• 期刊: The Journal of the American Osteopathic Association.
• 作者: Balin,BJ;Appelt,DM
• 通讯作者: Appelt,DM

Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis.

巨细胞动脉炎中树突状细胞与活化的 CD4 T 细胞共定位。

• 发表时间: 2003
• 期刊: Clinical and experimental rheumatology
• 影响因子: 3.7
• 作者: Wagner,AD;Wittkop,U;Prahst,A;Schmidt,WA;Gromnica-Ihle,E;Vorpahl,K;Hudson,AP;Zeidler,H
• 通讯作者: Zeidler,H