Indiana Alzheimer's Disease Research Center

印第安纳阿尔茨海默病研究中心

• 批准号: 10666607
• 负责人: ANDREW J SAYKIN
• 金额: $ 298.82万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666607
• 关键词: Acceleration; Address; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease related dementia; Animal Model; Awareness; Biological; Biological Markers; Biological Models; Brain; Caregivers; Clinical; Clinical Trials; Cognition; Collaborations; Communities; Complex; Creativeness; DNA sequencing; Data; Data Science; Data Scientist; Dementia; Development; Diagnosis; Discipline; Disease; Disparity; Early Diagnosis; Early Intervention; Education; Environment; Environmental Risk Factor; Etiology; Family; Family member; Fostering; Functional disorder; Genetic; Goals; Growth; Healthcare; Heterogeneity; Image; Impaired cognition; Indiana; Individual; Industry; Informatics; Inherited; Institution; Interdisciplinary Study; International; Intervention; Leadership; Machine Learning; Maps; Methodology; Methods; Molecular; Molecular Genetics; Nature; Nerve Degeneration; Participant; Pathogenesis; Pathway interactions; Patients; Persons; Phase; Phenotype; Population Heterogeneity; Positioning Attribute; Positron-Emission Tomography; Prevalence; Prevention; Process; Proteomics; Research; Research Infrastructure; Research Personnel; Resource Development; Resources; Risk; Role; Science; Scientific Advances and Accomplishments; Scientist; Staging; Symptoms; Systems Biology; Targeted Research; Therapeutic; Thinking; Training and Education; Translational Research; Translations; Underrepresented Populations; Universities; academic program; advanced analytics; biological heterogeneity; brain health; caregiver interventions; clinical phenotype; cognitive testing; cohort; collaborative approach; cost effective; demented; disparity reduction; dosage; early detection biomarkers; effective therapy; ethnoracial; improved; induced pluripotent stem cell; innovation; lifestyle factors; medical schools; medical specialties; member; metabolomics; method development; mild cognitive impairment; multimodal neuroimaging; multiple omics; neuropathology; new therapeutic target; non-drug; novel; novel diagnostics; novel strategies; pharmacologic; pre-clinical; precision medicine; prevent; programs; recruit; socioeconomic diversity; stem; success; successful intervention; tau Proteins; therapeutic development; tool development; training opportunity; transcriptome sequencing; translational scientist

Project Summary – IADRC Overall The Indiana Alzheimer’s Disease Research Center (IADRC) was established in 1991 to bring investigators and institutional resources at the Indiana University School of Medicine (IUSM) together to address the fundamental causes and treatment of Alzheimer’s disease (AD) and related dementias (ADRD). Despite many important gains, the need for targeted research is greater than ever, with an estimated 5.8 million people in the U.S. suffering from AD/ADRD. Unfortunately, we do not yet know how to prevent AD or have an approved disease modifying intervention. Both are critical to stem the growth in dementia prevalence. The overarching goal of the IADRC going forward is to support the goal of the NAPA to prevent and effectively treat AD by 2025, through innovative research on etiology, early detection, and therapeutics. Biomarker studies indicate that processes leading to AD begin at least 20 years prior to dementia, suggesting that successful interventions must be implemented early. This presents a potential opportunity for early intervention, but the field is challenged by critical barriers decreasing the prospects of timely success. The IADRC has identified the barriers as: a) The current understanding of etiology and pathophysiology is fragmented and incomplete; b) Sensitive, specific, and cost-effective methods for early detection are not available; c) Therapeutic development is hampered by the heterogeneity and complexity of ADRD; d) Shortage of data and translational scientists; and, e) Inadequate diversity at all levels. The IADRC specific aims entail innovation to overcome these barriers and accelerate research toward prevention and effective treatment: 1) Support, enhance, and expand innovative research on ADRD targeting causes, diagnosis, treatment, and prevention; 2) Provide critical research resources and infrastructure to support existing studies and enable new innovative research, utilizing a well-characterized longitudinal clinical cohort, with prioritization of diverse populations including underrepresented groups (URG) and those in preclinical and early symptomatic phases, including subjective cognitive decline and mild cognitive impairment, which will help to advance the identification of easily accessible biomarkers for early detection; 3) Identify and prioritize novel therapeutic targets from high-throughput approaches with rapid translation to proof- of-concept studies using genetic and other enrichment strategies for better biological targeting and reduction of phenotypic and biological heterogeneity for more efficient and cost-effective clinical trials; 4) Increase the number of investigators with deep expertise in advanced data sciences to bridge cellular/molecular processes of neurodegeneration and clinical phenotypes, as well as clinical and translational researchers who can move therapeutic approaches from model systems to clinical trials; 5) Provide educational and training opportunities related to dementia for a broad array of learners, with special emphasis on increasing participation from URG in ADRD related research and healthcare specialties. The IADRC is well-positioned to help achieve the NIA/NAPA goals through sustained and impactful contributions towards prevention and treatment of AD/ADRD.

项目总结 – IADRC 总体 印第安纳州阿尔茨海默病研究中心 (IADRC) 成立于 1991 年，旨在吸引研究人员和 印第安纳大学医学院 (IUSM) 的机构资源共同解决基本问题 阿尔茨海默病（AD）和相关痴呆症（ADRD）的病因和治疗有许多重要的内容。 随着进步的增加，对有针对性的研究的需求比以往任何时候都更大，估计美国有 580 万人。 不幸的是，我们还不知道如何预防 AD 或罹患 AD/ADRD 疾病。 改变干预措施对于遏制痴呆症患病率的增长至关重要。 IADRC 未来的目标是支持 NAPA 的目标，即到 2025 年预防和有效治疗 AD，方法是： 病因学、早期检测和治疗学的创新研究表明了这一过程。 导致AD至少在痴呆前20年开始，这表明成功的干预措施必须 这为早期干预提供了潜在的机会，但该领域面临着以下挑战： IADRC 已将障碍确定为： a) 目前对病因和病理生理学的理解是支离破碎且不完整的； b) 敏感、具体和不完整； 没有经济有效的早期检测方法； c) 治疗方法的开发受到阻碍 ADRD 的异质性和复杂性； d) 数据和转化科学家的短缺；以及 e) 不足 IADRC 的具体目标需要创新来克服这些障碍并加速发展。 预防和有效治疗的研究： 1) 支持、加强和扩大以下方面的创新研究 ADRD 针对病因、诊断、治疗和预防；2) 提供关键的研究资源和 基础设施，以支持现有研究并实现新的创新研究，利用特征良好的 纵向临床队列，优先考虑不同人群，包括代表性不足的群体 (URG) 以及处于临床前和早期症状阶段的患者，包括主观认知能力下降和轻度认知能力下降 损伤，这将有助于促进易于获取的生物标志物的识别，以进行早期检测；3) 从高通量方法中识别并优先考虑新的治疗靶点，并快速转化为证据- 使用遗传和其他富集策略进行概念研究，以实现更好的生物靶向和减少 表型和生物异质性，以实现更高效、更具成本效益的临床试验 4) 增加数量； 拥有先进数据科学深厚专业知识的研究人员，以桥接细胞/分子过程 神经退行性疾病和临床表型，以及可以移动的临床和转化研究人员 从模型系统到临床试验的治疗方法；5）提供教育和培训机会； 与广泛学习者的痴呆症相关，特别强调增加 URG 的参与 ADRD 相关研究和医疗保健专业能够帮助实现 NIA/NAPA。 通过对 AD/ADRD 的预防和治疗做出持续和有影响力的贡献来实现目标。

项目成果

Accelerating diversity in Alzheimer's disease research by partnering with a community advisory board.

• DOI: 10.1002/trc2.12400
• 发表时间: 2023-04
• 期刊: ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
• 影响因子: 4.8
• 作者: Pena-Garcia, Alex;Richards, Ralph;Richards, Mollie;Campbell, Christopher;Mosley, Hank;Asper, Joseph;Eliacin, Johanne;Polsinelli, Angelina;Apostolova, Liana;Hendrie, Hugh;Tackett, Andrew;Elliott, Caprice;Van Heiden, Sarah;Gao, Sujuan;Saykin, Andrew;Wang, Sophia
• 通讯作者: Wang, Sophia

Identifying brain hierarchical structures associated with Alzheimer's disease using a regularized regression method with tree predictors.

• DOI: 10.1111/biom.13775
• 发表时间: 2023-09
• 期刊: BIOMETRICS
• 影响因子: 1.9
• 作者: Zhao, Yi;Wang, Bingkai;Liu, Chin-Fu;Faria, Andreia, V;Miller, Michael, I;Caffo, Brian S.;Luo, Xi
• 通讯作者: Luo, Xi

Paravascular fluid dynamics reveal arterial stiffness assessed using dynamic diffusion-weighted imaging.

血管旁流体动力学揭示了使用动态扩散加权成像评估的动脉僵硬度。

• DOI: 10.1002/nbm.5048
• 发表时间: 2024
• 期刊: NMR in biomedicine
• 影响因子: 2.9
• 作者: Wen,Qiuting;Wright,Adam;Tong,Yunjie;Zhao,Yi;Risacher,ShannonL;Saykin,AndrewJ;Wu,Yu-Chien;Limaye,Kaustubh;Riley,Kalen
• 通讯作者: Riley,Kalen

Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19.

• DOI: 10.1097/cce.0000000000000851
• 发表时间: 2023-01
• 期刊: Critical care explorations

Cryo-EM structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy.

• DOI: 10.1186/s40478-023-01694-8
• 发表时间: 2023-12-04
• 期刊: Acta neuropathologica communications
• 影响因子: 7.1
• 作者: Yang Y;Murzin AG;Peak-Chew S;Franco C;Garringer HJ;Newell KL;Ghetti B;Goedert M;Scheres SHW
• 通讯作者: Scheres SHW