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ACS Nano. 2020 Mar 24. doi: 10.1021/acsnano.9b08572. [Epub ahead of print]

Identifying Fibrillization State of Aβ Protein via Near-Field THz Conductance Measurement.

Heo C1,2, Ha T1, You C2,3, Huynh T2,3, Lim H4, Kim J5, Kesama MR1,2, Lee J2,4, Kim TT1, Lee YH1,6.

Author information

1
Center for Integrated Nanostructure Physics (CINAP), Institute for Basic Science (IBS), Suwon 16419, Republic of Korea.
2
Institute for Quantum Biophysics (IQB), Sungkyunkwan University, Suwon 16419, Republic of Korea.
3
Department of Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea.
4
Department of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
5
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea.
6
Department of Energy Science and Department of Physics, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Abstract

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 < De < 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.

KEYWORDS:

Alzheimer’s disease; Drude−Smith model; amyloid beta (Aβ) protein; conductance; dementia; terahertz near-field spectroscopy

PMID:
32167289
DOI:
10.1021/acsnano.9b08572

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