Neurobiology of Mild Cognitive Impairment

描述（由申请人提供）：阿尔茨海默病是一种毁灭性的神经退行性疾病，影响美国500多万老年人，目前尚无治疗方法。必须确定最早的细胞机制， 最早发病的痴呆症，以开发新的疾病修饰治疗方法。标题为“老年人轻度认知障碍的神经生物学”的PPG的主旨仍然是阐明从无认知障碍（NCI）到轻度认知障碍（MCI）的细胞和分子基础或事件链，该时间点被认为是最可能的治疗窗口。此外，我们将重新集中精力纳入病理学提示AD的NCI受试者，以解决临床前AD的神经致病性后遗症。我们将实施一系列以胆碱能基底前脑皮层（CBF）投射系统为中心的相互关联的基于回路的项目，该系统显示MCI（临床前AD）之前的早期细胞病理学，在临床痴呆的发病中起着关键作用， 是目前FDA批准的大多数AD药物的基础。针对该计划项目的竞争性更新申请提出的研究汇集了来自芝加哥和大学以外的一些基础和临床科学家，以研究与前驱AD（轻度认知障碍）相比，在称为临床前AD的疾病进展的非常早期阶段基于回路的神经元系统功能障碍。该计划项目包括一个具有临床/组织分布组件的管理核心以及一个统计和数据管理核心。此外，以下四个研究项目完成该计划：1）Tau异常和老年人轻度认知障碍（Lester“Skip”Binder，西北大学医学院）; 2）老年人中与神经病理学相关的神经病理学和轻度认知障碍（James Lah，埃默里大学医学院）; 3）老年人胆碱能基底前脑神经营养性功能障碍与轻度认知功能障碍（Elliott Mufson，Rush Medical Center）;和老年人的突触性断离和轻度认知障碍（Milos Ikonomovic，University of Pittsburgh）。每个核心支持所有研究项目，所有项目相互作用。

DESCRIPTION (provided by applicant): Alzheimer's disease is a devastating eurodegenerative disorder affecting more than 5 million older people in the U.S.A. for which there is not treatment. It is imperative to define the earliest cellular, mechanisms that drive the earliest onset of dementia in order to develop novel disease modifying therapeutic approaches. The thrust of this PPG entitled "Neurobiology of Mild Cognitive Impairment in the Elderly" continues to be to elucidate the cellular and molecular basis or chain of events leading from no cognitive impairment (NCI) to mild cognitive impairment (MCI), the time-point considered the most likely therapeutic window. Moreover, we will refocus our efforts to include NCI subjects with pathology suggestive of AD, in order to resolve the neuropathogenic sequela underlying preclinical AD. We will implement a series of interrelated circuit-based projects centered on the cholinergic basal forebrain cortical (CBF) projection system, which displays early cellular pathology prior to MCI (preclinical AD), plays a pivotal role in the onset of clinical dementia and is the basis for most of the current FDA approved drugs for AD. The investigations proposed for this competitive renewal application of the Program Project brings together a number of basic and clinician scientists from Chicago and outside universities to investigate circuit based neuronal system dysfunction at a very early stage in the disease progress termed preclinical AD compared to prodromal AD (mild cognitive impairment). The Program Project consists of an Administrative Core with a Clinical/Tissue Distribution component and a Statistics and Data Management Core. In addition the following four research projects complete the program: 1) Tau abnormalities and Mild Cognitive Impairment in the Elderly (Lester "Skip" Binder, Northwestern University Medical School); 2) Age-Related Neuropathology and Mild Cognitive Impairment in the Elderly (James Lah, Emory University School of Medicine); 3) Cholinergic Basal Forebrain Neurotrophic Abnormalities and Mild Cognitive Impairment in the Elderly (Elliott Mufson, Rush Medical Center); and Synaptic Abnormalities and Mild Cognitive Impairment in the Elderly (Milos Ikonomovic, University of Pittsburgh). Each core supports all research projects and all projects interact.