Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo
Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo
复制标题
DOI：
10.1038/nm1438
复制
发表时间：
2006-07-01
期刊：
影响因子：
82.9
通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
--
作者：
Bateman, Randall J.;Munsell, Ling Y.;Holtzman, David M.
某些疾病状态的特征是蛋白质的产生、积累或清除受到干扰。在阿尔茨海默病中，淀粉样蛋白b （A β）在大脑中的积累和淀粉样蛋白前体蛋白或产生A β的酶的致病突变表明A β的产生或清除失调。然而，A β合成或清除失调是否导致最常见形式的阿尔茨海默病（散发性，占病例的99%）尚不清楚。在这里，我们描述了一种方法来确定蛋白质的生产和清除率在人类中枢神经系统（CNS）。我们报告了A β在人体中枢神经系统体内的分式生产和清除率的首次测量结果，分别为7.6% /小时和8.3% /小时。该方法可用于寻找新的疾病生物标志物，评估导致疾病的蛋白质代谢的潜在差异，并根据其对提出的致病途径的药效学作用来评估治疗。
Certain disease states are characterized by disturbances in production, accumulation or clearance of protein. In Alzheimer disease, accumulation of amyloid-b (A beta) in the brain and disease-causing mutations in amyloid precursor protein or in enzymes that produce A beta indicate dysregulation of production or clearance of A beta. Whether dysregulation of A beta synthesis or clearance causes the most common form of Alzheimer disease (sporadic, > 99% of cases), however, is not known. Here, we describe a method to determine the production and clearance rates of proteins within the human central nervous system (CNS). We report the first measurements of the fractional production and clearance rates of A beta in vivo in the human CNS to be 7.6% per hour and 8.3% per hour, respectively. This method may be used to search for novel biomarkers of disease, to assess underlying differences in protein metabolism that contribute to disease and to evaluate treatments in terms of their pharmacodynamic effects on proposed disease-causing pathways.