Inflammatory cells and mediators in early stages of Alzhiemer's disease

描述：（改编自应用程序） 老年对照受试者的神经病理学检查和 来自巴尔的摩纵向研究队列的阿尔茨海默病（AD） 老年痴呆症（BLSA）和老年痴呆症？美国疾病研究中心（ADRC）的队列研究显示， 揭示了AD的病变先于痴呆的发作多年， 也许几十年，认知能力下降的开始是暂时的， 与老年斑中小胶质细胞活化的出现有关。这些 初步观察，与报告一致， 降低AD的风险和进展速度，表明炎症在AD中起着重要作用。 在AD的发病机制中起重要作用。此外，神经病理学 研究表明炎症细胞、补体和细胞因子的激活 老年斑中。然而，以前的研究只检查了大脑， 在AD的晚期在项目4中，他们建议审查早期 发展AD病变的大脑，重点是激活 星形胶质细胞和小胶质细胞，可能是对AB沉积的反应， 产生能够扩增补体的补体因子和细胞因子， 炎症反应和损害神经元和突触。具体目标1、 他们将研究小胶质细胞激活和大脑皮层 体积、海马和ERC中的神经元数量以及认知的变化。 具体目标2侧重于星形胶质细胞的激活及其产生的 补体因子和细胞因子（白细胞介素-6 [IL-6]、粒细胞巨噬细胞 集落刺激因子[GM-CSF]和单核细胞趋化蛋白 [MCP-1]），其可以吸引并激活老年斑中的小胶质细胞。具体 目的3：探讨小胶质细胞因子表达与胶质细胞增殖的关系， IL-1 α、IL-1 B、TNF-α与神经元和突触变性相关， 通过末端转移酶介导的脱氧尿苷测定AD 三磷酸-生物素缺口末端标记（TUNEL）的神经元和水平 突触素

DESCRIPTION: (Adapted from the application) Neuropathological examinations of older control subjects and cases of Alzheimer's disease (AD) from the cohorts of the Baltimore Longitudinal Study of Aging (BLSA) and Alzheimer?s Disease Research Center (ADRC) cohorts has revealed that the lesions of AD precede the onset of dementia by many years, and perhaps decades, and that the onset of cognitive decline is temporally related to the appearance of microglial activation in senile plaques. These preliminary observations, in concert with reports that anti-inflammatory drugs reduce the risk and rate of progression of AD, suggest that inflammation plays a significant role in the pathogenesis of AD. Moreover, neuropathological studies have shown activation of inflammatory cells, complement, and cytokines in senile plaques in AD. However, previous studies have only examined brains in advanced stages of AD. In Project 4, they propose to examine the early development of AD lesions in the brain, focusing on the activation of astrocytes and microglia, perhaps in response to AB deposition, and the production of complement factors and cytokines capable of amplifying an inflammatory reaction and damaging neurons and synapses. In Specific Aim 1, they will examine the relationships between microglial activation and cortical volume, number of neurons in hippocampus and ERC, and changes in cognition. Specific Aim 2 focuses on the activation of astrocytes and their production of complement factors and cytokines (interleukin-6 [IL-6], granulocyte macrophage colony-stimulating factor [GM-CSF], and monocyte chemoattractant protein [MCP-1]) that may attract and activate microglia in senile plaques. Specific Aim 3 examines the hypotheses that the expression of microglial cytokines (IL-1a, IL-1 B, TNF-a) correlates with neuronal and synaptic degeneration in AD as measured by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) of neurons and levels of synaptophysin.