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Sci Adv. 2019 Apr 17;5(4):eaav1388. doi: 10.1126/sciadv.aav1388. eCollection 2019 Apr.

Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system.

Kim Y1,2,3, Yoo YK4,5, Kim HY2,3, Roh JH6, Kim J7, Baek S2,3,8,9, Lee JC1,2,3, Kim HJ4, Chae MS4, Jeong D4, Park D4, Lee S2,3,9, Jang H2,3,9, Kim K2,3, Lee JH5, Byun BH10, Park SY11, Ha JH11, Lee KC12, Cho WW13, Kim JS14, Koh JY6, Lim SM11, Hwang KS4.

Author information

1
Integrated Science and Engineering Division, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
2
Department of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
3
Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
4
Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
5
Department of Electrical Engineering, Kwangwoon University, 20 Kwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.
6
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.
7
Department of Medical Biotechnology, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul 04620, Republic of Korea.
8
Department of Biotechnology, Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul 03722, Republic of Korea.
9
Brain Science Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
10
Department of Nuclear Medicine, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
11
Department of Neurology of Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
12
Division of RI-Convergence Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
13
Cantis, Sangnok-gu, Ansan-si, Gyeonggi-do 15588, Republic of Korea.
14
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.

Abstract

Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Here, we introduce a diagnostic technique that compares the heterogeneous and the monomerized states of Aβ in plasma. We used a small molecule, EPPS [4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid], to dissociate aggregated Aβ into monomers to enhance quantification accuracy. Subsequently, Aβ levels of EPPS-treated plasma were compared to those of untreated samples to minimize inter- and intraindividual variations. The interdigitated microelectrode sensor system was used to measure plasma Aβ levels on a scale of 0.1 pg/ml. The implementation of this self-standard blood test resulted in substantial distinctions between patients with AD and individuals with normal cognition (NC), with selectivity and sensitivity over 90%.

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