Indiana Alzheimer's Disease Research Center

项目摘要-IADRC总体情况 印第安纳州阿尔茨海默病研究中心(IADRC)成立于1991年，旨在为研究人员和 印第安纳大学医学院(IUSM)的机构资源共同解决根本问题 阿尔茨海默病(AD)和相关痴呆(ADRD)的原因和治疗。尽管有许多重要的 随着研究成果的增加，对有针对性的研究的需求比以往任何时候都更大，美国估计有580万人。 患有AD/ADRD。不幸的是，我们还不知道如何预防阿尔茨海默病或已获批准的疾病 修改干预措施。两者对于遏制痴呆症患病率的增长都至关重要。的首要目标是 IADRC今后将支持国家适应行动方案的目标，即到2025年预防和有效治疗AD，通过 病因学、早期发现和治疗方面的创新研究。生物标记物研究表明，过程 导致AD至少在痴呆症发生前20年就开始了，这表明成功的干预措施必须是 提早实施。这为早期干预提供了一个潜在的机会，但该领域面临着 关键障碍降低了及时成功的前景。IADRC已确定这些障碍为：a) 目前对病因学和病理生理学的理解是支离破碎和不完整的；b)敏感、特异和 没有成本效益高的早期检测方法；c)治疗发展受到以下因素的阻碍 ADRD的异质性和复杂性；d)缺乏数据和翻译科学家；以及e)不足 各个层面的多样性。IADRC的具体目标要求进行创新，以克服这些障碍并加快 预防和有效治疗研究：1)支持、加强和扩大创新研究 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，以支持现有的研究和支持新的创新研究，利用具有良好特点的 纵向临床队列，包括代表性不足群体(URG)在内的不同人群的优先顺序 临床前和早期症状阶段，包括主观认知能力下降和轻度认知能力下降 损伤，这将有助于提前识别易于获得的生物标记物，以便及早发现；3) 通过快速转化为证据，从高通量方法中识别并优先处理新的治疗靶点- 使用遗传和其他浓缩策略进行概念研究，以更好地进行生物靶向和减少 表型和生物异质性，以实现更有效和更具成本效益的临床试验；4)增加数量 在高级数据科学方面拥有深厚专业知识的研究人员组成的团队，在细胞/分子过程之间架起桥梁 神经退行性变和临床表型，以及可以移动的临床和翻译研究人员 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 与痴呆症相关的广泛学习者，特别强调增加URG在 ADRD相关研究和保健专业。IADRC处于有利地位，可以帮助实现NIA/NAPA 通过对AD/ADRD的预防和治疗作出持续和有效的贡献，实现千年发展目标。

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.