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The apparent mechanical effect of isolated amyloid-β and α-synuclein aggregates revealed by multi-frequency MRE.
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2019-11-06 , DOI: 10.1002/nbm.4174
Mathilde Bigot 1 , Fabien Chauveau 2 , Camille Amaz 3 , Ralph Sinkus 4 , Olivier Beuf 1 , Simon A Lambert 1
Affiliation  

Several biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal-like properties of fibrils to separate them from nonaggregated proteins using a multi-frequency MRE power law exponent in a phantom study. Two types of fibril, α-synuclein (α-Syn) and amyloid-β (Aβ), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200 Hz. After 3D-direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α-Syn and Aβ inclusions showed significantly higher y values than control inclusions (P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α-Syn and Aβ aggregates, which was better captured with the power law exponent derived from multi-frequency MRE than with single frequency-derived parameters.

中文翻译:

多频MRE揭示了分离的淀粉样蛋白β和α-突触核蛋白聚集体的表观机械作用。

痴呆症涉及几种生物学过程,畸形内源蛋白的纤维状聚集似乎是神经退行性疾病的早期标志。研究神经退行性疾病的一种最新开发的手段是磁共振弹性成像(MRE),这是一种研究组织机械特性的成像技术。尽管已经检测到与这些疾病相关的机械变化,但是在临床或临床前研究中尚未分离出原纤维的特定信号。当前的研究旨在利用幻像研究中的多频MRE幂律指数,利用原纤维的分形特性将其与非聚集蛋白分离。两种类型的原纤维,α-突触核蛋白(α-Syn)和淀粉样-β(Aβ),以及一种非聚集蛋白,牛血清白蛋白,用作对照,被并入专用的非分散琼脂糖体模中。弹性成像是在400至1200 Hz之间的多个频率下进行的。经过3D直接反演后,计算出储能模量(G'),相角(φ),波速和幂律指数(y)。没有检测到G'和ϕ的显着变化。α-Syn和Aβ夹杂物均显示出比对照夹杂物显着更高的y值(P = 0.005),但彼此之间没有差异。当前的幻像研究强调了α-Syn和Aβ聚集体的特定生物力学作用,用多频MRE导出的幂律指数比用单频衍生参数更好地捕获了该效应。计算出储能模量(G'),相角(φ),波速和幂律指数(y)。没有检测到G'和ϕ的显着变化。α-Syn和Aβ夹杂物均显示出比对照夹杂物显着更高的y值(P = 0.005),但彼此之间没有差异。当前的幻像研究强调了α-Syn和Aβ聚集体的特定生物力学作用,用多频MRE导出的幂律指数比用单频衍生参数更好地捕获了该效应。计算出储能模量(G'),相角(φ),波速和幂律指数(y)。没有检测到G'和ϕ的显着变化。α-Syn和Aβ夹杂物均显示出比对照夹杂物显着更高的y值(P = 0.005),但彼此之间没有差异。当前的幻像研究强调了α-Syn和Aβ聚集体的特定生物力学作用,用多频MRE导出的幂律指数比用单频衍生参数更好地捕获了该效应。
更新日期:2019-12-20
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