Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

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Abstract

Background

Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer’s disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis.

Methods

We predicted the brain amyloid deposit by measuring the plasma Aβ levels. This cross-sectional study included 353 participants (215 cognitively normal, 79 with mild cognitive impairment, and 59 with AD dementia) who underwent Pittsburgh-compound B positron emission tomography (PiB-PET) scans. We treated a mixture of protease inhibitors and phosphatase inhibitors (MPP) and detected plasma Aβ42 and Aβ40 (MPP-Aβ42 and MPP-Aβ40) in a stable manner using xMAP technology.

Results

MPP-Aβ40 and MPP-Aβ42/40 (MPP-Aβs) were significantly different between subjects with positive amyloid deposition (PiB+) and those with negative amyloid deposition (PiB–) ( P < 0.0001). Furthermore, MPP-Aβ40 ( P < 0.0001, r = 0.23) and MPP-Aβ42/40 ratio ( P < 0.0001, r = –0.23) showed significant correlation with global PiB deposition (standardized uptake value ratio). In addition, our integrated multivariable (MPP-Aβ42/40, gender, age, and apolipoprotein E genotypes) logistic regression model proposes a new standard for the prediction of cerebral amyloid deposition.

Conclusions

MPP-Aβ might be one of the potential blood biomarkers for the prediction of PiB-PET positivity in the brain.

Electronic supplementary material

The online version of this article (doi:10.1186/s13195-017-0248-8) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Jong-Chan Park: fmly0614@snu.ac.kr

Sun-Ho Han: sunho@snu.ac.kr

Hyun Jin Cho: jeaniecho80@snu.ac.kr

Min Soo Byun: bminsoo@gmail.com

Dahyun Yi: dahyunyi@gmail.com

Young Min Choe: ymchoe7@gmail.com

Seokjo Kang: sjkang0420@snu.ac.kr

Eun Sun Jung: dalcomhae@snu.ac.kr

Su Jin Won: sjjsjjs@snu.ac.kr

Eun Hye Kim: ehkim0106@naver.com

Yu Kyeong Kim: yk3181@snu.ac.kr

Dong Young Lee: +82-2-2072-2205 , selfpsy@snu.ac.kr

Inhee Mook-Jung: +82-2-740-8245 , inhee@snu.ac.kr

Journal

Journal ID (nlm-ta): Alzheimers Res Ther

Journal ID (iso-abbrev): Alzheimers Res Ther

Title: Alzheimer's Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1758-9193

Publication date (Electronic): 22 March 2017

Publication date PMC-release: 22 March 2017

Publication date Collection: 2017

Volume: 9

Electronic Location Identifier: 20

Affiliations

[1 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Department of Biochemistry and Biomedical Sciences, , Seoul National University, College of Medicine, ; 103 Daehak-ro, Jongno-gu, Seoul, 110-799 South Korea

[2 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Neuroscience Research Institute, , Seoul National University, College of Medicine, ; 103 Daehak-ro, Jongno-gu, Seoul, 110-799 South Korea

[3 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Institute of Human Behavioral Medicine, , Medical Research Center Seoul National University, ; Seoul, 110-799 South Korea

[4 ]Department of Neuropsychiatry, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, 682-714 South Korea

[5 ]GRID grid.412479.d, Department of Nuclear Medicine, , Seoul Metropolitan Government–Seoul National University Boramae Medical Center, ; Seoul, 156-707 South Korea

[6 ]ISNI 0000 0001 0302 820X, GRID grid.412484.f, Department of Neuropsychiatry, , Seoul National University Hospital, ; 101 Daehak-ro, Jongno-gu, Seoul, 110-744 South Korea

[7 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Department of Psychiatry, , Seoul National University College of Medicine, ; 101 Daehak-ro, Jongno-gu, Seoul, 110-744 South Korea

Article

Publisher ID: 248

DOI: 10.1186/s13195-017-0248-8

PMC ID: 5361707

PubMed ID: 28330509

SO-VID: aa93e34b-de39-4502-b4f3-7af4eeeb52f7

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.