Prognostic plasma protein panel for Aβ deposition in the brain in Alzheimer's disease

Jong Chan Park, Sun Ho Han, Hangyeore Lee, Hyobin Jeong, Min Soo Byun, Jingi Bae, Hokeun Kim, Dong Young Lee, Dahyun Yi, Seong A. Shin, Yu Kyeong Kim, Daehee Hwang, Sang Won Lee, Inhee Mook-Jung

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    24 Citations (Scopus)

    Abstract

    Alzheimer's disease (AD) is the most common age-associated dementia. Many studies have sought to predict cerebral amyloid deposition, the major pathological hallmark of AD, using body fluids such as blood or cerebral spinal fluid (CSF). The use of blood in diagnostic procedures is widespread in medicine; however, existing blood biomarkers for AD remain unreliable. We sought to discover blood biomarkers that discriminate Aβ deposition status in the brain. This study used 107 individuals who were cognitively normal (CN), 107 patients with mild cognitive impairment (MCI), and 40 AD patients with Pittsburg compound B positron emission tomography (PiB-PET) amyloid imaging data available. We found five plasma biomarker candidates via mass spectrometry (MS) based-proteomic analysis and validated these proteins using enzyme-linked immunosorbent assay (ELISA). Our integrated models were highly predictive of brain amyloid deposition, exhibiting 0.871 accuracy with 79% sensitivity and 84% specificity overall, and 0.836 accuracy with 68% sensitivity and 90% specificity in patients with MCI. These results indicated that a combination of proteomic-based blood proteins might be a possible biomarker set for predicting cerebral amyloid deposition.

    Original languageEnglish
    Article number101690
    JournalProgress in Neurobiology
    Volume183
    DOIs
    Publication statusPublished - 2019 Dec

    Bibliographical note

    Funding Information:
    This work was supported in part by grants from the NRF funded by the Korean government (MSIP) (Nos. 2018R1A2A1A19019062 , 2014M3C7A1046047 , and 2018R1A5A2025964 ) to I. Mook-Jung; from the NRF funded by the Institute for Basic Science ( IBS-R013-A1 ) of the Ministry of Science, ICT and Future Planning to D. Hwang; from the NRF funded by the Collaborative Genome Program for Fostering New Post-Genome Industry ( NRF-2017M3C9A5031597 ) awarded through the National Research Foundation, which is funded by the Korean Ministry of Science and ICT (MSIT) to S-W. Lee; and from the Ministry of Science and ICT Republic of Korea ( NRF-2014M3C7A1046042 ) to D. Lee.

    Publisher Copyright:
    © 2019 Elsevier Ltd

    Keywords

    • Alzheimer's disease
    • Cerebral amyloid deposition
    • PiB-PET
    • Plasma biomarker
    • Proteomics
    • TMT

    ASJC Scopus subject areas

    • General Neuroscience

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