title: PiB-PET Imaging-Based Serum Proteome Profiles Predict Mild Cognitive Impairment and Alzheimer's Disease.
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.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Republic of Korea.
authors.forename: Seokjo
authors.initials: S
authors.lastname: Kang
authors.affiliation: Center for Systems Biology of Plant Senescence and Life History, Institute for Basic Science, Daegu, Republic of Korea.
authors.forename: Hyobin
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Republic of Korea.|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.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Center for Systems Biology of Plant Senescence and Life History, Institute for Basic Science, Daegu, Republic of Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Republic of Korea.
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Medifron DBT, Inc., Gyeongi, Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Medifron DBT, Inc., Gyeongi, Korea.
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Medifron DBT, Inc., Gyeongi, Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Yi
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.affiliation: Center for Systems Biology of Plant Senescence and Life History, Institute for Basic Science, Daegu, Republic of Korea.|Department of New Biology, DGIST, Daegu, Republic of Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Republic of Korea.
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000000981:diagnostic imaging*; D000814:Aniline Compounds; D001798:Blood Proteins / Q000378:metabolism*; D002853:Chromatography, Liquid; D060825:Cognitive Dysfunction / Q000097:blood* / Q000000981:diagnostic imaging*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005176:Factor XIII; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010455:Peptides; D049268:Positron-Emission Tomography; D000071449:Proprotein Convertase 9 / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D001798:Blood Proteins; D010455:Peptides; D013844:Thiazoles; C442243:dermcidin; D005176:Factor XIII; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Alzheimer’s disease; LC-MS/MS; biomarker; mild cognitive impairment; proteomics; serum