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首页> 外文期刊>Frontiers in Behavioral Neuroscience >The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome
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The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome

机译：唐氏综合症生物标志物倡议（DSBI）试点：唐氏综合症中阿尔茨海默氏病生物标志物深表型的概念验证

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To gain further knowledge on the preclinical phase of Alzheimer’s disease (AD), we sought to characterize cognitive performance, neuroimaging and plasma-based AD biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30–60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid positron emission tomography (PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and retinal amyloid imaging. In addition, plasma beta-amyloid (Aβ) species were measured and Apolipoprotein E (ApoE) genotyping was performed. Results from our multimodal analysis suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971.
机译：为了进一步了解阿尔茨海默氏病（AD）的临床前期，我们试图对一组患有唐氏综合症（DS）的非痴呆症成年人的认知表现，基于神经影像和血浆的AD生物标记物进行表征。唐氏综合症生物标志物计划（DSBI）试点的目标是测试此方法在未来多中心研究中的可行性。我们招募了12名30至60岁之间的非痴呆性DS参与者。与会者进行了广泛的认知测试，体积MRI，淀粉样蛋白正电子发射断层扫描（PET; 18F-florbetapir），氟脱氧葡萄糖（FDG）PET（18F-氟脱氧葡萄糖）和视网膜淀粉样蛋白成像。另外，测量血浆β-淀粉样蛋白（Aβ）种类并进行载脂蛋白E（ApoE）基因分型。我们的多模式分析结果表明，淀粉样蛋白负荷会导致海马萎缩。此外，我们发现淀粉样蛋白负荷与区域葡萄糖代谢之间存在反比关系。认知和功能指标与DS中淀粉样蛋白负荷无关，但与区域FDG PET指标相关。与其他临床前AD人群一样，在具有DS的成人中可以容易地研究AD的生物标记。重要的是，该可行性研究中的所有受试者都能够完成所有测试程序。数据表明，进行大规模，多中心的纵向研究对于更好地了解这一丰富人群中AD生物标志物的轨迹是可行的。该试验已在ClinicalTrials.gov上注册，编号为NCT02141971。

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