New Approaches to Dementia Heterogeneity

摘要 加州大学旧金山分校阿尔茨海默病研究中心(ADRC)是一种广泛的 在加州大学旧金山分校进行的痴呆症相关研究，已成为国家和国际 多点诊断和治疗研究。在P50机制之前的三个供资周期中，我们 组织了大量的痴呆症研究，并广泛分享我们的资源。我们在临床上表现出色 对早期和独特的大型队列进行表型、成像、生物样品收集和病理学评估。 发作性阿尔茨海默病(EoAD)、额颞叶痴呆(FTD)、进行性核上性瘫痪(PSP)、皮质基底膜 CBS综合征(CBS)、克雅病(CJD)和健康对照。ADRC支持并有效地 利用更多的NIH和基金会资金、慈善事业和行业合作来实现其 目标。仅在加州大学旧金山分校的记忆和衰老中心，ADRC的临床队列、数据和生物样本目前 由26个R拨款、6个K奖励、4个U拨款和38个非NIH拨款使用。项目和试点奖项起到了帮助 启动青年调查员职业生涯和重大研究项目。利用ADRC数据和生物样本 由其他区域发展研究中心和广泛的合作者网络广泛传播。 在这个新的P30应用程序中，我们加快了定义健康老龄化、MCI、AD、FTD、PSP、 CBS和CJD预测痴呆症的特定分子和生理原因，有助于早期识别 以及跟踪从正常衰老到痴呆症的转变，并刺激药物开发和临床试验。 ADRC将由七个核心组成：行政、临床、数据管理和统计、病理学、 外展招聘和接洽、成像和生物标记以及研究教育部分。这些 各核心部门将共同努力，以实现以下总体具体目标：目标1：探索异质 健康老龄化、MCI、AD、FTD谱系障碍和CJD的特征，以更好地了解他们的临床、遗传、 以及分子基础。目标2：利用ADRC中有价值的同龄人和有才华的神经科学 加州大学旧金山分校及其他地方的社区，围绕诊断和 痴呆症的治疗。目标3：增进对老龄化独特的文化和生物学特征的了解 华裔和拉丁裔美国人，同时通过外展讲座和基于网络的教育来教育这些社区 演示文稿。目标4：开发数据管理和生物统计的创新方法，以支持Easy 访问和分析ADRC相关数据，同时为我们的调查人员提供统计支持。目标5：培训 痴呆症研究领域的新领导者，采用创新的教育方法，教育医学和非传染性疾病 社区通过会议、基于网络的演示和电影了解痴呆症的异质性。 目标6：创建新的Biomarker Core以增强从以下来源获取的基因组、蛋白质组和转录组数据 我们丰富的生物标本收藏。目标7：向更具性别和种族多样性的非盟过渡 到2024年的领导力。

ABSTRACT The UCSF Alzheimer’s Disease Research Center (ADRC) is a major catalyst for a broad spectrum of dementia-related research conducted at UCSF and has served as a cornerstone for national and international multi-site diagnostic and treatment studies. In three previous cycles of funding under the P50 mechanism, we have organized a critical mass of dementia research and share our resources widely. We excel in clinical phenotyping, imaging, biospecimen collection, and pathologic evaluation of large and unique cohorts of early- onset AD (EOAD), frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Creutzfeldt-Jakob disease (CJD), and healthy controls. The ADRC supports and effectively leverages additional NIH and foundation funding, philanthropy, and industry collaborations to accomplish its aims. At the UCSF Memory and Aging Center alone, ADRC clinical cohorts, data, and biosamples are currently utilized by 26 R grants, 6 K awards, 4 U grants, and 38 non-NIH grants. Projects and pilot awards have helped launch young investigator careers and major research programs. ADRC data and biosamples are utilized extensively by other ADRCs and an extensive network of collaborators. In this new P30 application, we accelerate efforts to define subtypes of healthy aging, MCI, AD, FTD, PSP, CBS, and CJD that predict specific molecular and physiological causes for dementia, improve early recognition and tracking of transitions from normal aging to dementia, and stimulate drug development and clinical trials. The ADRC will consist of seven cores: Administrative, Clinical, Data Management and Statistics, Pathology, Outreach Recruitment and Engagement, Imaging, and Biomarker and a Research Education Component. These cores will work collectively to pursue the following overarching specific aims: Aim 1: Explore the heterogeneous features of healthy aging, MCI, AD, FTD-spectrum disorders, and CJD to better understand their clinical, genetic, and molecular underpinnings. Aim 2: Leverage the valuable cohorts in the ADRC and the talented neuroscience communities at UCSF and beyond to “enhance the performance of innovative research” around diagnosis and treatment of dementia. Aim 3: Increase understanding of the unique cultural and biological features of aging Chinese and Latino Americans, while educating these communities with outreach lectures and web-based presentations. Aim 4: Develop innovative approaches to data management and biostatistics to support easy access and analysis of ADRC-related data while offering statistical support to our investigators. Aim 5: Train new leaders in dementia research with innovative education approaches and educate medical and lay communities about the heterogeneity of dementia with conferences, web-based presentations, and films. Aim 6: Create a new Biomarker Core to enhance the genomic, proteomic, and transcriptomic data captured from our extensive biospecimen collection. Aim 7: Transition to a more gender and ethnically diverse ADRC leadership by 2024.