Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease.
Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease.
复制标题
DOI：
10.1001/jamaneurol.2015.0202
复制
发表时间：
2015-06
期刊：
影响因子：
29
通讯作者：
Holtzman DM
中科院分区：
文献类型：
--
作者：
Tarawneh R;Head D;Allison S;Buckles V;Fagan AM;Ladenson JH;Morris JC;Holtzman DM
神经元损失的测量可能是阿尔茨海默病（AD）临床和放射学疾病进展的良好替代物。神经元损伤或神经变性的脑脊液（CSF）标志物可用于预测疾病进展，并指导疾病缓解治疗临床试验的结局评估和预后决策。Visin-like protein 1（VILIP-1）作为AD神经元损伤的标志物具有潜在的应用价值。研究CSF VILIP-1、tau、p-tau 181和Aβ42水平在预测早期AD受试者和认知正常对照受试者随时间推移的全脑和局部萎缩率方面的有用性。早期AD患者和认知正常对照者脑萎缩的纵向观察研究研究参与者进行了基线CSF生物标志物测量和纵向磁共振成像评估，平均随访期为2至3年。混合线性模型评估了标准化基线CSF生物标志物测量预测随访期间全脑和局部萎缩率的能力。地点：The Charles F.和圣刘易斯的华盛顿大学医学院的乔安妮·奈特阿尔茨海默病研究中心。参与者（平均年龄，72.6岁）是临床诊断为非常轻度AD（n = 23）和认知正常对照（n = 64）的个体，他们参加了健康老龄化和痴呆的纵向研究。研究日期为2000年至2010年。随访期间AD和对照队列中基线CSF生物标志物测量值与全脑或局部萎缩率之间的相关性。基线CSF VILIP-1、tau和p-tau 181水平（而非Aβ42水平）可预测随访期间AD患者全脑和局部萎缩的发生率。基线CSF VILIP-1水平预测早期AD的全脑（P = .006）、海马（P = .01）和内嗅（P = .001）萎缩率至少与tau和p-tau 181一样。CSF VILIP-1、tau或p-tau 181水平在上三分位数的认知正常对照组，（分别为P = .02、P = .003和P = .02），海马（P = 0.001，P = 0.01，P = 0.02），和内嗅（P = 0.007，P = 0.01，P = 0.01，P = 0.01，分别）萎缩与那些水平在较低的2个三分位数。脑脊液VILIP-1水平与tau和p-tau 181类似地预测全脑和局部萎缩的发生率，并且可以为早期症状性和临床前AD中的神经变性提供有用的CSF生物标志物替代物。
Measures of neuronal loss are likely good surrogates for clinical and radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in predicting disease progression and guiding outcome assessments and prognostic decisions in clinical trials of disease-modifying therapies. Visinin-like protein 1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury in AD. To investigate the usefulness of CSF VILIP-1, tau, p-tau181, and Aβ42 levels in predicting rates of whole-brain and regional atrophy in early AD and cognitively normal control subjects over time. Longitudinal observational study of brain atrophy in participants with early AD and cognitively normal controls. Study participants had baseline CSF biomarker measurements and longitudinal magnetic resonance imaging assessments for a mean follow-up period of 2 to 3 years. Mixed linear models assessed the ability of standardized baseline CSF biomarker measures to predict rates of whole-brain and regional atrophy over the follow-up period. The setting was The Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine in St Louis. Participants (mean age, 72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23) and cognitively normal controls (n = 64) who were enrolled in longitudinal studies of healthy aging and dementia. The study dates were 2000 to 2010. Correlations between baseline CSF biomarker measures and rates of whole-brain or regional atrophy in the AD and control cohorts over the follow-up period. Baseline CSF VILIP-1, tau, and p-tau181 levels (but not Aβ42 levels) predicted rates of whole-brain and regional atrophy in AD over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P = .006), hippocampal (P = .01), and entorhinal (P = .001) atrophy rates at least as well as tau and p-tau181 in early AD. Cognitively normal controls whose CSF VILIP-1, tau, or p-tau181 levels were in the upper tercile had higher rates of whole-brain (P = .02, P = .003, and P = .02, respectively), hippocampal (P = .001, P = .01, and P = .02, respectively), and entorhinal (P = .007, P = .01, and P = .01, respectively) atrophy compared with those whose levels were in the lower 2 terciles. Cerebrospinal fluid VILIP-1 levels predict rates of whole-brain and regional atrophy similarly to tau and p-tau181 and may provide a useful CSF biomarker surrogate for neurodegeneration in early symptomatic and preclinical AD.