Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42

被引:56
作者
An, Seong Soo A. [1 ]
Lee, Byoung-sub [2 ]
Yu, Ji Sun [2 ]
Lim, Kuntaek [2 ]
Kim, Gwang Je [2 ]
Lee, Ryan [2 ]
Kim, Shinwon [2 ]
Kang, Sungmin [2 ]
Park, Young Ho [3 ,4 ]
Wang, Min Jeong [3 ,4 ]
Yang, Young Soon [5 ]
Youn, Young Chul [6 ]
Kim, SangYun [3 ,4 ]
机构
[1] Gachon Univ, Dept Bionanotechnol, Incheon, South Korea
[2] PeopleBio Inc, Res & Dev, Gyeonggi Do, South Korea
[3] Seoul Natl Univ, Dept Neurol, Coll Med, 300 Gumidong, Seongnam Si 463707, Gyeonggi Do, South Korea
[4] Seoul Natl Univ, Bundang Hosp, Neurocognit Behav Ctr, 300 Gumidong, Seongnam Si 463707, Gyeonggi Do, South Korea
[5] Vet Hlth Serv Med Ctr, Dept Neurol, Seoul, South Korea
[6] Chung Ang Univ, Dept Neurol, Coll Med, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Multimer detection system; Alzheimer's disease; Amyloid-beta; Oligomers; Blood biomarker; Synthetic amyloid-beta; ELISA; Plasma test; SOLUBLE-PROTEIN OLIGOMERS; NEURONAL THREAD PROTEIN; ALZHEIMERS-DISEASE; EARLY-DIAGNOSIS; BIOMARKERS; BRAIN; PEPTIDES; URINE; PREDICTION; MECHANISM;
D O I
10.1186/s13195-017-0310-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: A reliable blood-based assay is required to properly diagnose and monitor Alzheimer's disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-beta oligomers (A beta Os) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect A beta Os. Methods: To characterize A beta in the blood, plasma was spiked with synthetic amyloid-beta (A beta) and incubated over time. Then, the MDS was used to monitor the dynamic changes of A beta O levels in the plasma. Results: Increasing concentrations of A beta Os were observed in the plasma of patients with AD but not in the plasma of normal control subjects. The plasma from patients with AD (n = 27) was differentiated from that of the age-matched normal control subjects (n = 144) with a sensitivity of 83.3% and a specificity of 90.0%. Conclusions: Synthetic A beta spiked into the blood plasma of patients with AD, but that of not elderly normal control subjects, induced dynamic changes in the formation of A beta Os over time. A beta Os were detected by the MDS, which is a useful blood-based assay with high sensitivity and specificity for AD diagnosis.
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页数:10
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