Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans.
Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans.
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DOI：
10.1016/j.mbs.2014.11.004
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发表时间：
2015-03
影响因子：
4.3
通讯作者：
Bateman RJ
中科院分区：
文献类型：
--
作者：
Elbert DL;Patterson BW;Bateman RJ
β淀粉样蛋白（Aβ）肽，特别是Aβ42，存在于与阿尔茨海默病相关的老年斑中。最近开发了一个Aβ产生、交换和不可逆损失的房室模型，用于解释人体输注稳定同位素标记亮氨酸后脑脊液（CSF）中收集的Aβ肽的同位素标记动力学。房室模型允许计算Aβ肽的生产率、不可逆损失（或转换）和短期交换。Aβ42的交换在淀粉样斑块的参与者中特别明显。在目前的工作中，我们更详细地描述了两个不同的观众的房室模型的特点：物理学家，科学家和生物动力学。对于物理学家，我们通过例子描述了模型可以回答和不能回答的问题类型，以及纠正以前的动力学分析应用于这种类型的同位素标记数据的一些误解。对于生物动力学家，我们进行了系统的可识别性分析和灵敏度分析的动力学模型，探索该模型的全局和局部属性。结合起来，这些分析激励简化从一个更全面的生理模型的最终模型，以前提出的。分析清楚地表明，当前的数据集和分区模型可以自信地确定单个“交易额”参数、单个“交换”参数和单个“延迟”参数。当与Aβ肽的CSF浓度数据结合时，也可以获得生产率。
Amyloid beta (Aβ) peptides, and in particular Aβ42, are found in senile plaques associated with Alzheimer's disease. A compartmental model of Aβ production, exchange and irreversible loss was recently developed to explain the kinetics of isotope-labeling of Aβ peptides collected in cerebrospinal fluid (CSF) following infusion of stable isotope-labeled leucine in humans. The compartmental model allowed calculation of the rates of production, irreversible loss (or turnover) and short-term exchange of Aβ peptides. Exchange of Aβ42 was particularly pronounced in amyloid plaque-bearing participants. In the current work, we describe in much greater detail the characteristics of the compartmental model to two distinct audiences: physician-scientists and biokineticists. For physician-scientists, we describe through examples the types of questions the model can and cannot answer, as well as correct some misunderstandings of previous kinetic analyses applied to this type of isotope labeling data. For biokineticists, we perform a system identifiability analysis and a sensitivity analysis of the kinetic model to explore the global and local properties of the model. Combined, these analyses motivate simplifications from a more comprehensive physiological model to the final model that was previously presented. The analyses clearly demonstrate that the current dataset and compartmental model allow determination with confidence a single ‘turnover’ parameter, a single ‘exchange’ parameter and a single ‘delay’ parameter. When combined with CSF concentration data for the Aβ peptides, production rates may also be obtained.
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影响因子：
82.9
作者：
Bateman, Randall J.;Munsell, Ling Y.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
4.3
作者：
BELLMAN R;ASTROM K J
通讯作者：
ASTROM K J
影响因子：
4.7
作者：
Welander, Hedvig;Franberg, Jenny;Tjernberg, Lars O.
通讯作者：
Tjernberg, Lars O.
影响因子：
--
作者：
COBELLI, C;DISTEFANO, JJ
通讯作者：
DISTEFANO, JJ
影响因子：
17.1
作者：
Potter R;Patterson BW;Elbert DL;Ovod V;Kasten T;Sigurdson W;Mawuenyega K;Blazey T;Goate A;Chott R;Yarasheski KE;Holtzman DM;Morris JC;Benzinger TL;Bateman RJ
通讯作者：
Bateman RJ