Bateman Randall J, Munsell Ling Y, Morris John C, Swarm Robert, Yarasheski Kevin E, Holtzman David M
Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, Missouri 63110, USA.
Nat Med. 2006 Jul;12(7):856-61. doi: 10.1038/nm1438. Epub 2006 Jun 25.
Certain disease states are characterized by disturbances in production, accumulation or clearance of protein. In Alzheimer disease, accumulation of amyloid-beta (Abeta) in the brain and disease-causing mutations in amyloid precursor protein or in enzymes that produce Abeta indicate dysregulation of production or clearance of Abeta. Whether dysregulation of Abeta 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 Abeta 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.
某些疾病状态的特征是蛋白质的产生、积累或清除出现紊乱。在阿尔茨海默病中，淀粉样β蛋白（Aβ）在大脑中的积累以及淀粉样前体蛋白或产生Aβ的酶中的致病突变表明Aβ的产生或清除失调。然而，Aβ合成或清除的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%以上）尚不清楚。在这里，我们描述了一种确定人类中枢神经系统（CNS）内蛋白质产生和清除率的方法。我们报告了人类中枢神经系统中Aβ体内分数产生率和清除率的首次测量结果，分别为每小时7.6%和每小时8.3%。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潜在差异，并根据其对提出的致病途径的药效学作用评估治疗方法。
