New Approaches to Dementia Heterogeneity

痴呆症异质性的新方法

• 批准号: 10647902
• 负责人: Gil Dan Rabinovici
• 金额: $ 346.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10647902
• 关键词: Acceleration; Aging; Alzheimer' s Disease; American; Award; Basic Science; Biological; Biological Markers; Biology; Biometry; Caregiver support; Caring; Chinese; Clinical; Clinical Trials; Cognition Disorders; Collaborations; Collection; Communities; Creutzfeldt-Jakob Syndrome; Data; Dementia; Diagnosis; Diagnostic; Disease; Early Onset Alzheimer Disease; Education; Endowment; Evaluation; Film; Foundations; Frontotemporal Dementia; Funding; Generations; Genetic; Genomics; Grant; Heterogeneity; Image; Industry Collaboration; International; K-Series Research Career Programs; Knowledge; Latino; Lead; Leadership; Medical; Memory; Minority; Modeling; Molecular; Neurodegenerative Disorders; Neurologic; Neurologist; Neurosciences; Nurses; Online Systems; Pathologic; Pathology; Performance; Physiological; Policies; Population Heterogeneity; Process; Progressive Supranuclear Palsy; Proteomics; Public Health; Research; Research Personnel; Resources; Sampling; Science; Scientist; Site; Specialist; Specialized Center; Tablets; Talents; Tauopathies; Training; United States National Institutes of Health; Work; brain health; career; catalyst; clinical center; clinical diagnostics; clinical phenotype; cohort; community center; corticobasal syndrome; data management; data sharing; drug development; education research; ethnic diversity; gender diversity; health care delivery; health economics; health equity; healthy aging; improved; innovation; lectures; normal aging; novel; novel strategies; outreach; programs; recruit; statistics; symposium; tau Proteins; therapy development; transcriptomics; translational scientist

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.

抽象的 加州大学旧金山分校阿尔茨海默病研究中心 (ADRC) 是广泛领域的主要催化剂 加州大学旧金山分校进行的痴呆症相关研究已成为国内和国际研究的基石 在 P50 机制下的前三个资助周期中，我们进行了多中心诊断和治疗研究。 我们组织了大量的痴呆症研究并广泛共享我们的资源，我们在临床方面表现出色。 对大型且独特的早期疾病群体进行表型分析、成像、生物样本采集和病理评估 发病性 AD (EOAD)、额颞叶痴呆 (FTD)、进行性核上性麻痹 (PSP)、皮质基底节 综合征 (CBS)、克雅氏病 (CJD) 和健康对照 ADRC 支持并有效。 利用额外的 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记忆与衰老中心，目前就有 ADRC 临床队列、数据和生物样本。 26 个 R 资助、6 个 K 资助、4 个 U 资助和 38 个非 NIH 资助项目和试点资助提供了帮助。 启动年轻研究者职业生涯并利用 ADRC 数据和生物样本。 通常由其他 ADRC 和广泛的合作者网络进行。 在这个新的P30应用中，我们努力加速定义健康老龄化、MCI、AD、FTD、PSP、 CBS 和 CJD 可以预测痴呆症的特定分子和生理原因，提高早期识别能力 跟踪从正常衰老到痴呆的转变，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、 外展招募和参与、成像、生物标记以及研究教育部分。 核心将共同努力实现以下总体具体目标： 目标 1：探索异构 健康老龄化、MCI、AD、FTD 谱系疾病和 CJD 的特征，以更好地了解其临床、遗传、 目标 2：利用 ADRC 的宝贵团队和优秀的神经科学人才。 加州大学旧金山分校及其他社区围绕诊断和治疗“提高创新研究的绩效” 目标 3：增进对衰老独特文化和生物学特征的了解。 华人和拉美裔美国人，同时通过外展讲座和网络教育这些社区 目标 4：开发数据管理和生物统计学的创新方法，以支持轻松的工作。 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。 痴呆症研究的新领导者采用创新的教育方法并教育医学界和非专业人士 通过会议、网络演示和电影向社区介绍痴呆症的异质性。 目标 6：创建新的生物标记核心，以增强从基因组、蛋白质组和转录组中捕获的数据 我们广泛的生物样本收藏 目标 7：向性别和种族更加多元化的 ADRC 过渡。 到 2024 年保持领先地位。

项目成果

Chronic Traumatic Encephalopathy: A Comparison with Alzheimer's Disease and Frontotemporal Dementia.

慢性创伤性脑病：与阿尔茨海默病和额颞叶痴呆的比较。

• DOI: 10.1055/s-0040-1715134
• 发表时间: 2020
• 期刊: Seminars in neurology
• 影响因子: 2.7
• 作者: Lesman-Segev,OritH;Edwards,Lauren;Rabinovici,GilD
• 通讯作者: Rabinovici,GilD

Understanding social attachment as a window into the neural basis of prosocial behavior.

• DOI: 10.3389/fneur.2023.1247480
• 发表时间: 2023
• 期刊: Frontiers in neurology
• 影响因子: 3.4

Co-pathology may impact outcomes of amyloid-targeting treatments: clinicopathological results from two patients treated with aducanumab.

• DOI: 10.1007/s00401-023-02631-8
• 发表时间: 2023-11
• 期刊: Acta neuropathologica
• 影响因子: 12.7

Rapid Isolation of Functional Synaptic Vesicles from Tissues Through Cryogrinding, Ultracentrifugation, and Size Exclusion Chromatography.

通过冷冻研磨、超速离心和尺寸排阻色谱从组织中快速分离功能性突触小泡。

• DOI: 10.1007/978-1-0716-1916-2_10
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Li,Huinan

Corticobasal syndrome with visual hallucinations and probable REM-sleep behavior disorder: an autopsied case report of a patient with CBD and LBD pathology.

皮质基底节综合征伴视幻觉和可能的快速眼动睡眠行为障碍：一名患有 CBD 和 LBD 病理学的患者的尸检病例报告。

• DOI: 10.1080/13554794.2019.1604973
• 发表时间: 2019
• 期刊: Neurocase
• 影响因子: 0.8
• 作者: Naasan,George;Shany-Ur,Tal;Sidhu,Manu;Barton,Cynthia;Ketelle,Robin;Shdo,SuzanneM;Kramer,JoelH;Miller,BruceL;Seeley,WilliamW
• 通讯作者: Seeley,WilliamW