4.6 Article

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

Journal

ALZHEIMERS RESEARCH & THERAPY
Volume 9, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s13195-017-0248-8

Keywords

Alzheimer's disease; beta-amyloid; Plasma A beta; Blood-based biomarker; MPP; Pittsburgh-compound B positron emission tomography

Funding

  1. NRF [2015R1A2A1A05001794, 2014M3C-7A1046047, 2014M3C7A1046042, 2015R1C1A2A01053545]
  2. MRC [2011-0030738]
  3. SNU Medical School Basic-clinical [800-20130066, 800-20130067]
  4. Education and Research Encouragement Fund of SNU Hospital for IHM-J
  5. National Research Foundation of Korea [2015R1C1A2A01053545] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Background: Plasma beta-amyloid (A beta) 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 A beta is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma A beta levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma A beta levels in the blood of patients with AD. If a consistent value of plasma A beta from the blood can be obtained, this might help determine whether plasma A beta is a potential biomarker for AD diagnosis. Methods: We predicted the brain amyloid deposit by measuring the plasma A beta 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 A beta 42 and A beta 40 ( MPP-A beta 42 and MPP-A beta 40) in a stable manner using xMAP technology. Results: MPP-A beta 40 and MPP-A beta 42/40 (MPP-A beta s) were significantly different between subjects with positive amyloid deposition (PiB+) and those with negative amyloid deposition (PiB-) (P < 0.0001). Furthermore, MPP-A beta 40 (P < 0.0001, r = 0.23) and MPP-A beta 42/40 ratio (P < 0.0001, r = -0.23) showed significant correlation with global PiB deposition (standardized uptake value ratio). In addition, our integrated multivariable (MPP-A beta 42/40, gender, age, and apolipoprotein E genotypes) logistic regression model proposes a new standard for the prediction of cerebral amyloid deposition. Conclusions: MPP-A beta might be one of the potential blood biomarkers for the prediction of PiB-PET positivity in the brain.

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