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

Title
PiB-PET Imaging-Based Serum Proteome Profiles Predict Mild Cognitive Impairment and Alzheimer's Disease
Author(s)
Kang, SeokjoJeong, HyobinBaek, Je-HyunLee, Seung-JinHan, Sun-HoCho, Hyun JinKim, HeeHong, Hyun SeokKim, Young HoYi, Eugene C.Seo, Sang WonNa, Duk L.Hwang, DaeheeMook-Jung, Inhee
Issued Date
2016
Citation
Journal of Alzheimers Disease, v.53, no.4, pp.1563 - 1576
Type
Article
Author Keywords
Alzheimer&aposs diseasebiomarkerLC-MS/MSmild cognitive impairmentproteomicsserum
Keywords
Alzheimer&aposs DiseaseAlzheimer DiseaseArticleBiological MarkerBiomarkerBiomarkersBlood Clotting Factor xIIi A1 PolypeptideBlood SamplingBrain ScintiscanningBrain TissueCEREBROSPINAL-FLUIDControlled StudyDATABASEDermcidinEarly DiagnosisEnzyme Linked Immunosorbent AssayEXPRESSIONGene ExpressionGene IdentificationGene OntologyGenomicsHumanIntegrationLC-MS/MSLiquid ChromatographyMASS-SPECTROMETRYMild Cognitive ImpairmentMolecular PathologyMOUSE MODELNeuropathologyPITTSBURGH COMPOUND-BPittsburgh Compound BPositron emission TomographyPriority JournalProprotein Convertase Subtilisin Kexin Type 9Protein Blood LevelProtein DegradationProtein Protein InteractionPROTEOMEProteomicsSERUMSYSTemS-APPROACHTANDEM MASS-SPECTROMETRYTRAFFICKINGUnclassified DrugUp-RegulationWestern Blotting
ISSN
1387-2877
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.
URI
http://hdl.handle.net/20.500.11750/2765
DOI
10.3233/JAD-160025
Publisher
Institute of Physics Publishing
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Department of New Biology Systems Biology and Medicine Lab 1. Journal Articles

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