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

• Published in: Science advances Vol. 5; no. 4; p. eaav1388
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01-04-2019
• Subjects: Aged; Alzheimer Disease - blood; Alzheimer Disease - pathology; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - chemistry; Animals; Disease Models, Animal; Female; Humans; Immunoassay - instrumentation; Immunoassay - methods; Lab-On-A-Chip Devices; Limit of Detection; Magnetic Resonance Imaging; Male; Mice; Mice, Transgenic; Microelectrodes; Middle Aged; Neuroscience; Piperazines - chemistry; Positron-Emission Tomography; Radiopharmaceuticals - chemistry; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aav1388

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%.