New Approaches to Dementia Heterogeneity

描述（由申请人提供）：本提案的目的是在加州大学旧金山分校（UCSF）建立一个新的阿尔茨海默病研究中心（ADRC）。UCSF ADRC建议整合基础科学和临床资源，研究阿尔茨海默病（AD）、非AD性痴呆和轻度认知障碍（MCI）的临床、分子、神经病理和神经影像学特征。拟议的ADRC有两个总体目标：1)弥合痴呆和衰老的实验室和临床研究之间的差距；2)探索不同神经退行性疾病的早期、异质性和重叠表现。新的ADRC将帮助整合强大的UCSF基础科学和临床神经学项目，以促进新的发现。为了实现这些目标，ADRC将围绕五个核心和三个项目进行组织。行政、教育和外展核心将提供全面管理、培训和少数民族外展方面的支持。临床核心将保持AD、额颞叶变性、进行性核上性麻痹、皮质基底变性、克雅氏病和MCI患者的良好特征队列。将研究AD和MCI的非典型表现，特别关注具有孤立语言或执行症状的患者。数据管理和生物统计核心将确保数据的标准化收集、验证和新颖的统计分析。神经病理学中心将从ADRC队列中获取尸检材料，并促进临床病理研究。神经成像核心将使用4特斯拉MRI来研究痴呆症的鉴别诊断。一个项目将开发新的试剂来研究PrPC的结构和评估蛋白质检测小鼠PrPsc的能力。第二个项目将评估小鼠和人类认知缺陷与钙依赖蛋白之间的关系。最终项目将使用来自加利福尼亚州阿尔茨海默病中心的1061例MCI病例的独特队列数据来确定结果、风险因素和MCI亚型。本项目还将评估遗忘型和非遗忘型（语言型、执行型和混合型）轻度认知损伤患者，以更好地定义轻度认知损伤的异质性。因此，新的ADRC将以UCSF的现有优势为基础，促进AD和非AD痴呆以及MCI的独特研究，这将对当地和全国产生影响。

DESCRIPTION (provided by applicant): The purpose of this proposal is to establish a new Alzheimer's Disease Research Center (ADRC) at the University of California, San Francisco (UCSF). The UCSF ADRC proposes to integrate basic science and clinical resources to investigate the clinical, molecular, neuropathological and neuroimaging features of Alzheimer's disease (AD), non-AD dementias, and mild-cognitive impairment (MCI). The proposed ADRC has two overarching aims: 1) to bridge the gap between laboratory and clinical studies in dementia and aging and 2) to explore the early, heterogeneous and overlapping presentations of different neurodegenerative disorders. The new ADRC will help integrate the strong UCSF basic science and clinical neurology programs in an effort to promote new discoveries. To address these aims, the ADRC will be organized around five Cores and three Projects. The Administrative, Education and Outreach Core will provide support overall management, training, and minority outreach. The Clinical Core will maintain well characterized cohorts of patients with AD, frontotemporal lobar degeneration, progressive supranuclear palsy, corticobasal degeneration, Creutzfeldt-Jakob disease, and MCI. Atypical presentations of AD and MCI will be studied, with special interest in patients with isolated language or executive symptoms. The Data Management and Biostatistical Core will assure standardized collection, validation, and novel statistical analysis of data. The Neuropathology Core will obtain autopsy material from the ADRC cohorts and facilitate clinicopathological studies. The Neuroimaging Core will use 4 Tesla MRI to investigate differential diagnosis of dementia. One Project will develop novel reagents to study PrPC structure and evaluate the ability of proteins to detect PrPsc in mice. A second Project will evaluate the relationship between cognitive deficits and calcium-dependent proteins in mice and humans. The final Project will use data from a unique cohort of 1061 MCI cases from the State of California's Alzheimer's Disease Centers to identify outcomes, risk factors, and MCI subtypes. This Project will also evaluate amnestic and nonamnestic (language, executive and mixed) MCI patients in an effort to better define the heterogeneity of MCI. The new ADRC will, therefore, build upon existing strengths at UCSF to promote unique studies of AD and non-AD dementias and MCI that will have an impact both locally and nationally.