PiB-PET Imaging-Based Serum Proteome Profiles Predict Mild Cognitive Impairment and Alzheimer’s Disease

Article type: Research Article

Authors: Kang, Seokjo^{a; 1} | Jeong, Hyobin^{b; 1} | Baek, Je-Hyun^{a; d} | Lee, Seung-Jin^b | Han, Sun-Ho^a | Cho, Hyun Jin^a | Kim, Hee^c | Hong, Hyun Seok^c | Kim, Young Ho^c | Yi, Eugene C.^d | Seo, Sang Won^{e; f; g} | Na, Duk L.^{e; f; g} | Hwang, Daehee^{b; h; *} | Mook-Jung, Inhee^{a; *}

Affiliations: [a] Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Republic of Korea | [b] Center for Systems Biology of Plant Senescence and Life History, Institute for Basic Science, Daegu, Republic of Korea | [c] Medifron DBT, Inc., Gyeongi, Korea | [d] Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea | [e] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [f] Neuroscience Center, Samsung Medical Center, Seoul, Korea | [g] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea | [h] Department of New Biology, DGIST, Daegu, Republic of Korea

Correspondence: [*] Correspondence to: Inhee Mook-Jung, PhD, Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul 110-799, Republic of Korea. Tel.: +82 2 740 8245; Fax: +82 2 3672 7352;E-mail: [email protected].

Correspondence: [*] Correspondence to: Daehee Hwang, PhD, Department of New Biology and Center for Plant Aging Research, Institute of Basic Science, DGIST, Daegu, 711-873, Republic of Korea. Tel.: +82 53 785 1840; Fax: +82 53 785 1809; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Development of a simple, non-invasive early diagnosis platform of Alzheimer’s disease (AD) using blood is urgently required. Recently, PiB-PET imaging has been shown to be powerful to quantify amyloid-β plaque loads leading to pathophysiological alterations in AD brains. Thus, there has been a need for serum biomarkers reflecting PiB-PET imaging data as an early diagnosis platform of AD. Here, using LC-MS/MS analysis coupled with isobaric tagging, we performed comprehensive proteome profiling of serum samples from cognitively normal controls, mild cognitive impairment (MCI), and AD patients, who were selected using PiB-PET imaging. Comparative analysis of the proteomes revealed 79 and 72 differentially expressed proteins in MCI and AD, respectively, compared to controls. Integrated analysis of these proteins with genomic and proteomic data of AD brain tissues, together with network analysis, identified three biomarker candidates representing the altered proteolysis-related process in MCI or AD: proprotein convertase subtilisin/kexin type 9 (PCSK9), coagulation factor XIII, A1 polypeptide (F13A1), and dermcidin (DCD). In independent serum samples of MCI and AD, we confirmed the elevation of the candidates using western blotting and ELISA. Our results suggest that these biomarker candidates can serve as a potential non-invasive early diagnosis platform reflecting PiB-PET imaging for MCI and AD.

Keywords: Alzheimer’s disease, biomarker, LC-MS/MS, mild cognitive impairment, proteomics, serum

DOI: 10.3233/JAD-160025

Journal: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1563-1576, 2016