Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition.
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.
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Jong-Chan
JC
Park
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.|Neuroscience Research Institute, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Sun-Ho
SH
Han
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Hyun Jin
HJ
Cho
Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, 110-799, South Korea.
Min Soo
MS
Byun
Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, 110-799, South Korea.
Dahyun
D
Yi
Department of Neuropsychiatry, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, 682-714, South Korea.
Young Min
YM
Choe
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Seokjo
S
Kang
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Eun Sun
ES
Jung
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Su Jin
SJ
Won
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Eun Hye
EH
Kim
Department of Nuclear Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, 156-707, South Korea.
Yu Kyeong
YK
Kim
Department of Neuropsychiatry, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. selfpsy@snu.ac.kr.|Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. selfpsy@snu.ac.kr.
Dong Young
DY
Lee
Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea. inhee@snu.ac.kr.|Neuroscience Research Institute, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea. inhee@snu.ac.kr.
Inhee
I
Mook-Jung
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000097:blood*; D000814:Aniline Compounds; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000097:blood / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D058225:Plaque, Amyloid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000188:drug therapy; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
Alzheimer’s disease; Blood-based biomarker; MPP; Pittsburgh-compound B positron emission tomography; Plasma Aβ; β-amyloid