一种无标记X射线方法用于估计小动物脑淀粉样蛋白负荷的可行性。

Feasibility of a label-free X-ray method to estimate brain amyloid load in small animals.

作者信息

Dahal Eshan, Ghammraoui Bahaa, Badano Aldo

机构信息

Division of Imaging, Diagnostics, and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.

出版信息

J Neurosci Methods. 2020 Sep 1;343:108822. doi: 10.1016/j.jneumeth.2020.108822. Epub 2020 Jun 20.

DOI:10.1016/j.jneumeth.2020.108822

PMID:32574641

Abstract

BACKGROUND

Amyloid plaque in the brain is associated with a wide range of neurodegenerative diseases such as Alzheimer's and Parkinson's and defined as aggregates of amyloid fibrils rich in β-sheet structures.

NEW METHOD

We report a label-free method based on small-angle X-ray scattering (SAXS) to estimate amyloid load in an intact mouse head with skull. The method is based on recording and analyzing the X rays elastically scattered from the β-sheets of amyloid plaques in a mouse head at angles smaller than 10° and energies between 30 and 45 keV. The method is demonstrated by acquiring the spectral SAXS data of an amyloid model and an excised head from a wild-type mouse for 600 s.

RESULTS

We captured the distinct scattering peaks of the amyloid plaques at momentum transfer (q) of 6 and 13 nm associated with β-sheet structure. We first show linear correlation between the mass fraction of the amyloid target and the area under the peak (AUP) of the scattering curve. We report results for estimating amyloid load in a fixed mouse head by recovering the characteristic scattering signal from the amyloid target situated at various locations. The coefficient of variation in the amyloid load estimate is found to be less than 10%.

COMPARISON WITH EXISTING METHODS

There are no previously described label-free X-ray methods for the estimation of amyloid load in an intact head.

CONCLUSIONS

We demonstrated the feasibility of a label-free method based on SAXS to potentially estimate brain amyloid in small animals.

摘要

背景

大脑中的淀粉样斑块与多种神经退行性疾病相关，如阿尔茨海默病和帕金森病，其被定义为富含β-折叠结构的淀粉样纤维聚集体。

新方法

我们报告了一种基于小角X射线散射（SAXS）的无标记方法，用于估计完整带颅骨小鼠头部的淀粉样蛋白负荷。该方法基于记录和分析在小于10°的角度以及30至45 keV能量下从小鼠头部淀粉样斑块的β-折叠弹性散射的X射线。通过获取淀粉样蛋白模型和野生型小鼠切除头部600秒的光谱SAXS数据来证明该方法。

结果

我们在与β-折叠结构相关的动量转移（q）为6和13 nm处捕捉到了淀粉样斑块的明显散射峰。我们首次展示了淀粉样蛋白靶标的质量分数与散射曲线的峰下面积（AUP）之间的线性相关性。我们报告了通过从位于不同位置的淀粉样蛋白靶标恢复特征散射信号来估计固定小鼠头部淀粉样蛋白负荷的结果。发现淀粉样蛋白负荷估计中的变异系数小于10%。