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

YoungSoo Kim, Yong Kyoung Yoo, Hye Yun Kim, Jee Hoon Roh, Jinsik Kim, Seungyeop Baek, Jinny Claire Lee, Hye Jin Kim, Myung-Sic Chae, Dahye Jeong, Dongsung Park, Sejin Lee, HoChung Jang, Kyeonghwan Kim, Jeong Hoon Lee, Byung Hyun Byun, Su Yeon Park, Jeong Ho Ha, Kyo Chul Lee, Won Woo ChoJae-Seung Kim, Jae-Young Koh, Sang Moo Lim, Kyo Seon Hwang

Research output: Contribution to journalArticle

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%.

Original languageEnglish
Pages (from-to)eaav1388
JournalScience Advances
Volume5
Issue number4
DOIs
Publication statusPublished - 2019 Apr 17

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Microelectrodes
Amyloid
Alzheimer Disease
Acids
Hematologic Tests
Blood-Brain Barrier
Cognition
Disease Progression

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Kim, YoungSoo ; Yoo, Yong Kyoung ; Kim, Hye Yun ; Roh, Jee Hoon ; Kim, Jinsik ; Baek, Seungyeop ; Lee, Jinny Claire ; Kim, Hye Jin ; Chae, Myung-Sic ; Jeong, Dahye ; Park, Dongsung ; Lee, Sejin ; Jang, HoChung ; Kim, Kyeonghwan ; Lee, Jeong Hoon ; Byun, Byung Hyun ; Park, Su Yeon ; Ha, Jeong Ho ; Lee, Kyo Chul ; Cho, Won Woo ; Kim, Jae-Seung ; Koh, Jae-Young ; Lim, Sang Moo ; Hwang, Kyo Seon. / Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system. In: Science Advances. 2019 ; Vol. 5, No. 4. pp. eaav1388.
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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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Kim, Y, Yoo, YK, Kim, HY, Roh, JH, Kim, J, Baek, S, Lee, JC, Kim, HJ, Chae, M-S, Jeong, D, Park, D, Lee, S, Jang, H, Kim, K, Lee, JH, Byun, BH, Park, SY, Ha, JH, Lee, KC, Cho, WW, Kim, J-S, Koh, J-Y, Lim, SM & Hwang, KS 2019, 'Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system', Science Advances, vol. 5, no. 4, pp. eaav1388. https://doi.org/10.1126/sciadv.aav1388

Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system. / Kim, YoungSoo; Yoo, Yong Kyoung; Kim, Hye Yun; Roh, Jee Hoon; Kim, Jinsik; Baek, Seungyeop; Lee, Jinny Claire; Kim, Hye Jin; Chae, Myung-Sic; Jeong, Dahye; Park, Dongsung; Lee, Sejin; Jang, HoChung; Kim, Kyeonghwan; Lee, Jeong Hoon; Byun, Byung Hyun; Park, Su Yeon; Ha, Jeong Ho; Lee, Kyo Chul; Cho, Won Woo; Kim, Jae-Seung; Koh, Jae-Young; Lim, Sang Moo; Hwang, Kyo Seon.

In: Science Advances, Vol. 5, No. 4, 17.04.2019, p. eaav1388.

Research output: Contribution to journalArticle

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AU - Kim, Hye Yun

AU - Roh, Jee Hoon

AU - Kim, Jinsik

AU - Baek, Seungyeop

AU - Lee, Jinny Claire

AU - Kim, Hye Jin

AU - Chae, Myung-Sic

AU - Jeong, Dahye

AU - Park, Dongsung

AU - Lee, Sejin

AU - Jang, HoChung

AU - Kim, Kyeonghwan

AU - Lee, Jeong Hoon

AU - Byun, Byung Hyun

AU - Park, Su Yeon

AU - Ha, Jeong Ho

AU - Lee, Kyo Chul

AU - Cho, Won Woo

AU - Kim, Jae-Seung

AU - Koh, Jae-Young

AU - Lim, Sang Moo

AU - Hwang, Kyo Seon

PY - 2019/4/17

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N2 - 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%.

AB - 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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DO - 10.1126/sciadv.aav1388

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