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阿尔茨海默病的数学模型

Mathematical model on Alzheimer's disease.

作者信息

Hao Wenrui, Friedman Avner

机构信息

Department of Mathematics, The Penn State University, University Park, 16802, PA, USA.

Mathematical Biosciences Institute & Department of Mathematics, The Ohio State University, Columbus, 43210, OH, USA.

出版信息

BMC Syst Biol. 2016 Nov 18;10(1):108. doi: 10.1186/s12918-016-0348-2.

Abstract

BACKGROUND

Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease. If no cure is found, by 2050 the number of alzheimer's patients in the U.S. will reach 15 million and the cost of caring for them will exceed $ 1 trillion annually.

RESULTS

The present paper develops a mathematical model of AD that includes neurons, astrocytes, microglias and peripheral macrophages, as well as amyloid β aggregation and hyperphosphorylated tau proteins. The model is represented by a system of partial differential equations. The model is used to simulate the effect of drugs that either failed in clinical trials, or are currently in clinical trials.

CONCLUSIONS

Based on these simulations it is suggested that combined therapy with TNF- α inhibitor and anti amyloid β could yield significant efficacy in slowing the progression of AD.

摘要

背景

阿尔茨海默病(AD)是一种进行性神经退行性疾病,会破坏记忆和认知能力。AD的特征是存在两种神经病理学特征:由淀粉样β肽组成的细胞外斑块和过度磷酸化tau蛋白的细胞内神经原纤维缠结。该疾病在美国影响500万人,在全球影响4400万人。目前尚无药物能够治愈、阻止甚至减缓该疾病的进展。如果找不到治愈方法,到2050年,美国阿尔茨海默病患者数量将达到1500万,每年照顾他们的费用将超过1万亿美元。

结果

本文建立了一个AD数学模型,该模型包括神经元、星形胶质细胞、小胶质细胞和外周巨噬细胞,以及淀粉样β聚集和过度磷酸化tau蛋白。该模型由一个偏微分方程组表示。该模型用于模拟在临床试验中失败或目前正在进行临床试验的药物的效果。

结论

基于这些模拟结果,建议联合使用TNF-α抑制剂和抗淀粉样β治疗可能在减缓AD进展方面产生显著疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eecd/5116206/ab8b4bcc4230/12918_2016_348_Fig1_HTML.jpg

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