DOMINANTLY INHERITED ALZHEIMER NETWORK TRIAL: AN OPPORTUNITY TO PREVENT DEMENTIA

显性遗传性阿尔茨海默病网络试验：预防痴呆症的机会

基本信息

批准号：
8506912
负责人：
RANDALL J BATEMAN
金额：
$ 150万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-20 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8506912
关键词：
Accounting Alzheimer disease prevention Alzheimer&apos s Disease Amyloid Amyloid beta-Protein Precursor Amyloidosis Animal Model Antibodies Antibody Formation Atrophic Biochemical Biological Biological Markers Blinded Blood Brain Cell model Cerebrospinal Fluid Chronic Clinical Clinical Trials Clinical Trials Design Cognitive Collection Cross-Sectional Studies Data Set Dementia Development Disease Enrollment Functional disorder Funding Future Genes Goals Grant Health Image Impaired cognition Individual Inherited Interest Group International Liquid substance Metabolic Modification Molecular Monoclonal Antibodies Mutation Nature Nerve Degeneration Onset of illness Oral Outcome Participant Patients Performance Pharmaceutical Preparations Pharmacologic Substance Phase Phenotype Placebo Control Placebos Population Positron-Emission Tomography Prevention Probability Process Production Protocols documentation Randomized Recruitment Activity Registries Research Research Infrastructure Risk Staging Symptoms Testing Therapeutic Time United States National Institutes of Health amyloid imaging arm base beta secretase beta-site APP cleaving enzyme 1 brain volume design drug testing effective therapy four-arm study glucose metabolism improved inhibitor/antagonist injection/infusion meetings mutation carrier presenilin-1 presenilin-2 prevent primary outcome randomized placebo controlled trial response secondary outcome tau Proteins therapeutic effectiveness

项目摘要

DESCRIPTION (provided by applicant): Autosomal dominant Alzheimer's disease (AD) has informed the field of AD research about the molecular and biochemical mechanisms that are believed to underlie the pathological basis of AD. Further, mutations from autosomal dominant AD have provided animal and cellular models that are utilized to develop anti-A¿ drugs. Due to the rarity of autosomal dominant AD, the Dominantly Inherited Alzheimer Network (DIAN; U01 AG032438) was launched in 2008 to establish an international, multicenter registry of individuals at risk or with a known causative mutation of AD in the amyloid precursor protein (APP), presenilin 1 (PS1), or presenilin 2 (PS2) genes. DIAN evaluates participants at entry and longitudinally thereafter with clinical and cognitive batteries, structural, functional, metabolic,and amyloid imaging protocols, and biological fluid (blood; cerebrospinal fluid) collection with the goal of determining the sequence of imaging and biomarker changes in presymptomatic gene carriers who are destined to develop AD. Because the clinical and pathological phenotypes of dominantly inherited AD appear similar to those for the far more common late-onset "sporadic" AD, the nature and sequence of brain changes in dominantly inherited AD are also likely relevant for sporadic AD. The trial design is a randomized, blinded placebo controlled four arm trial of a fibrillar anti-A¿ antibody, a soluble anti-A¿ antibody, and a beta-secretase inhibitor i 160 (n=40 per arm) asymptomatic to mildly symptomatic ADAD mutation carriers. Subjects will receive either drug of placebo for two years to determine engagement of the CNS mechanism of action and downstream AD biomarkers.

描述（由适用提供）：常染色体显性阿尔茨海默氏病（AD）已将AD研究领域告知有关分子和生化机制，这些机制被认为是AD病理基础的基础。此外，常染色体显性AD的突变提供了用于开发抗A抗药物的动物和细胞模型。由于常染色体显性AD的稀有性，2008年启动了主要继承的阿尔茨海默氏症网络（Dian; U01 AG032438），以建立一个具有风险或已知严重AD的个体的多中心注册表，该注册表中的AD（App）蛋白质（App），Protursor 1（PS1）（PS1）（PS1）（PS1），或PSCORSOR 2（PS）2（PS）2（PS）2（PS）。戴安（Dian）在进入和纵向上的参与者之后，通过临床和认知电池，结构，功能，代谢和淀粉样蛋白成像方案以及生物脊髓液（血液；脑脊液）收集的目的，以确定成像和生物标志物的序列和生物标志物的序列变化的目标，这些都是构成基因携带者的序列。由于主要遗传AD的临床和病理表型似乎与更常见的晚期发作的“零星” AD相似，因此大脑变化的性质和序列主要遗传的AD可能与零星的AD有关。该试验设计是一项随机的，盲目的安慰剂控制的四臂试验，该试验的原纤维抗A抗体，固体抗A抗体和β-分泌酶抑制剂I 160（每臂n = 40 n = 40）渐近地对称对称性ADAD突变载体。受试者将接受两年的安慰剂药物，以确定CNS作用机理和下游AD生物标志物的参与。