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

经化学处理的血浆 Aβ 是筛查脑淀粉样蛋白沉积的潜在血液生物标志物

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作者:Jong-Chan Park, Sun-Ho Han, Hyun Jin Cho, Min Soo Byun, Dahyun Yi, Young Min Choe, Seokjo Kang, Eun Sun Jung, Su Jin Won, Eun Hye Kim, Yu Kyeong Kim, Dong Young Lee, Inhee Mook-Jung

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.

Conclusions

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

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.

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