Neurobiology of Mild Cognitive Impairment

描述(申请人提供)：阿尔茨海默病是一种破坏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。当务之急是定义最早的细胞，驱动 最早发病的痴呆症，以开发新的疾病修改治疗方法。这篇题为《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，这一时间点被认为是最有可能的治疗窗口。此外，我们将重新集中精力，纳入有AD病理征象的NCI受试者，以解决潜在AD的神经致病后遗症。我们将实施一系列相关的基于电路的项目，以胆碱能基底前脑皮质(CBF)投射系统为中心，该系统在临床前阿尔茨海默病(MCI)之前显示早期细胞病理，在临床痴呆的发病中发挥关键作用。 是目前FDA批准的大多数AD药物的基础。该计划的竞争性续签申请建议的调查汇集了来自芝加哥和外部大学的许多基础和临床科学家，以研究在疾病进展的非常早期阶段基于电路的神经系统功能障碍，称为临床前AD与前驱AD(轻度认知障碍)的比较。该方案项目由一个行政核心、一个临床/组织分布部分和一个统计和数据管理核心组成。此外，以下四个研究项目还完成了该项目：1)老年人中的Tau异常和轻度认知障碍(西北大学医学院的Lester“Skip”Binder)；2)与年龄相关的神经病理和老年人中的轻度认知障碍(James Lah，埃默里大学医学院)；3)老年人中的胆碱能基础前脑神经营养异常和轻度认知障碍(Elliott Mufson，拉什医学中心)；以及老年人中的突触异常和轻度认知障碍(匹兹堡大学Milos Ikonomovic)。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.