Heo Chaejeong, Ha Taewoo, You Chunjae, Huynh Thuy, Lim Hosub, Kim Jiwon, Kesama Mallikarjuna Reddy, Lee Jinkee, Kim Teun-Teun, Lee Young Hee
Center for Integrated Nanostructure Physics (CINAP), Institute for Basic Science (IBS), Suwon 16419, Republic of Korea.
Institute for Quantum Biophysics (IQB), Sungkyunkwan University, Suwon 16419, Republic of Korea.
ACS Nano. 2020 Jun 23;14(6):6548-6558. doi: 10.1021/acsnano.9b08572. Epub 2020 Mar 24.
Progressive Alzheimer's disease is correlated with the oligomerization and fibrillization of the amyloid beta (Aβ) protein. We identify the fibrillization stage of the Aβ protein through label-free near-field THz conductance measurements in a buffer solution. Frequency-dependent conductance was obtained by measuring the differential transmittance of the time-domain spectroscopy in the THz range with a molar concentration of monomer, oligomer, and fibrillar forms of the Aβ protein. Conductance at the lower frequency limit was observed to be high in monomers, reduced in oligomers, and dropped to an insulating state in fibrils and increased proportionally with the Aβ protein concentration. The monotonic decrease in the conductance at low frequency was dominated by a simple Drude component in the monomer with concentration and nonlinear conductance behaviors in the oligomer and fibril. By extracting the structural localization parameter, a dimensionless constant, with the modified Drude-Smith model, we defined a dementia quotient (DQ) value (0 < < 1) as a discrete metric for a various Aβ proteins at a low concentration of 0.1 μmol/L; DQ = 1.0 ± 0.002 (fibril by full localization, mainly by Smith component), DQ = 0.64 ± 0.013 (oligomer by intermixed localization), and DQ = 0.0 ± 0.000 (monomer by Drude component). DQ values were discretely preserved independent of the molar concentration or buffer variation. This provides plenty of room for the label-free diagnosis of Alzheimer's disease using the near-field THz conductance measurement.
进行性阿尔茨海默病与淀粉样β（Aβ）蛋白的寡聚化和纤维化相关。我们通过在缓冲溶液中进行无标记近场太赫兹电导测量来确定Aβ蛋白的纤维化阶段。通过测量太赫兹范围内时域光谱的差分透射率，获得了单体、寡聚体和纤维化形式的Aβ蛋白在摩尔浓度下的频率依赖性电导。观察到在低频极限处，单体的电导较高，寡聚体的电导降低，而原纤维的电导降至绝缘状态，并与Aβ蛋白浓度成比例增加。低频下电导的单调下降在单体中由简单的德鲁德分量主导，在寡聚体和原纤维中则表现为非线性电导行为。通过用改进的德鲁德-史密斯模型提取结构定位参数（一个无量纲常数），我们定义了一个痴呆商（DQ）值（0 << 1）作为在0.1 μmol/L低浓度下各种Aβ蛋白的离散度量；DQ = 1.0 ± 0.002（完全定位的原纤维，主要由史密斯分量主导），DQ = 0.64 ± 0.013（混合定位的寡聚体），DQ = 0.0 ± 0.000（德鲁德分量主导的单体）。DQ值独立于摩尔浓度或缓冲液变化而离散保留。这为使用近场太赫兹电导测量进行阿尔茨海默病的无标记诊断提供了很大空间。
