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A highly sensitive plasma-based amyloid-β detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer's disease.

ABSTRACT: We developed an interdigitated microelectrode (IME) sensor system for blood-based Alzheimer's disease (AD) diagnosis based on impedimetric detection of amyloid-β (Aβ) protein, which is a representative candidate biomarker for AD. The IME sensing device was fabricated using a surface micromachining process. For highly sensitive detection of several tens to hundreds of picogram/mL of Aβ in blood, medium change from plasma to PBS buffer was utilized with signal cancellation and amplification processing (SCAP) system. The system demonstrated approximately 100-folds higher sensitivity according to the concentrations. A robust antibody-immobilization process was used for stability during medium change. Selectivity of the reaction due to the affinity of Aβ to the antibody and the sensitivity according to the concentration of Aβ were also demonstrated. Considering these basic characteristics of the IME sensor system, the medium change was optimized in relation to the absolute value of impedance change and differentiated impedance changes for real plasma based Aβ detection. Finally, the detection of Aβ levels in transgenic and wild-type mouse plasma samples was accomplished with the designed sensor system and the medium-changing method. The results confirmed the potential of this system to discriminate between patients and healthy controls, which would enable blood-based AD diagnosis.

SUBMITTER: Yoo YK

PROVIDER: S-EPMC5567090 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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A highly sensitive plasma-based amyloid-β detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer's disease.

Yoo Yong Kyoung YK Kim Jinsik J Kim Gangeun G Kim Young Soo YS Kim Hye Yun HY Lee Sejin S Cho Won Woo WW Kim Seongsoo S Lee Sang-Myung SM Lee Byung Chul BC Lee Jeong Hoon JH Hwang Kyo Seon KS

Scientific reports 20170821 1

We developed an interdigitated microelectrode (IME) sensor system for blood-based Alzheimer's disease (AD) diagnosis based on impedimetric detection of amyloid-β (Aβ) protein, which is a representative candidate biomarker for AD. The IME sensing device was fabricated using a surface micromachining process. For highly sensitive detection of several tens to hundreds of picogram/mL of Aβ in blood, medium change from plasma to PBS buffer was utilized with signal cancellation and amplification proces ...[more]

PMID: 28827785

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Project description:BACKGROUND: Amyloid precursor protein (APP), a key molecule in Alzheimer's disease (AD), is metabolized in two alternative cleavages, generating either the amyloidogenic peptides involved in AD pathology or the soluble form of APP (sAPP?). The level of amyloidogenic peptides in human cerebrospinal fluid (CSF) is considered to be a biomarker of AD, whereas the level of sAPP? in CSF as a biomarker has not been clearly established. sAPP? has neurotrophic and neuroprotective properties. Stimulating its formation and secretion is a promising therapeutic target in AD research. To this end, very sensitive tests for preclinical and clinical research are required. METHODS: The tests are based on homogenous time-resolved fluorescence and require no washing steps. RESULTS: We describe two new rapid and sensitive tests for quantifying mouse and human sAPP?. These 20 ?l-volume tests quantify the levels of: i) endogenous mouse sAPP? in the conditioned medium of mouse neuron primary cultures, as well as in the CSF of wild-type mice, ii) human sAPP? in the CSF of AD mouse models, and iii) human sAPP? in the CSF of AD and non-AD patients. These tests require only 5??l of conditioned medium from 5 × 10(4) mouse primary neurons, 1??l of CSF from wild-type and transgenic mice, and 0.5??l of human CSF. CONCLUSIONS: The high sensitivity of the mouse sAPP? test will allow high-throughput investigations of molecules capable of increasing the secretion of endogenous sAPP? in primary neurons, as well as the in vivo validation of molecules of interest through the quantification of sAPP? in the CSF of treated wild-type mice. Active molecules could then be tested in the AD mouse models by quantifying human sAPP? in the CSF through the progression of the disease. Finally, the human sAPP? test could strengthen the biological diagnosis of AD in large clinical investigations. Taken together, these new tests have a wide field of applications in preclinical and clinical studies.

Dataset Information

A highly sensitive plasma-based amyloid-β detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer's disease.

Publications

A highly sensitive plasma-based amyloid-β detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer's disease.

Similar Datasets

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