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140725_Sunil_iTRAQ_AD_08_C.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_15_B.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_05_B.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_02_B.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_18_C.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_12_A.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_19_A.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_02_A.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD012203/140725_Sunil_iTRAQ_AD_09_A.rawprimaryOK200102390sksze@ntu.edu.sgSunil AdavMass SpectrometryShotgun proteomicsAlzheimer's DiseaseNot availableHuman brainhttp://www.ebi.ac.uk/pride/archive/projects/PXD012203BrainFrozen individual brain samples were thawed on ice and equal quantity was pooled in a group-wise manner. The individual clinical details of the patients are listed in Table 1. The brain tissue samples from each patient and control (in equal quantity) were pooled together within the group. We pooled two brain tissues in early onset AD and their age-matched control while old onset AD and control include five-tissue specimen. The tissue samples were homogenized. in a urea-acetate buffer (8M urea, 100 mM ammonium acetate, pH 6.0) to prevent asparagine deamidation. The cell debris was removed by centrifugation at 5000 x g for 7 min at 4º C. The proteins were purified by acetone precipitation and 200 µg proteins from each group were loaded into 12.5% SDS-PAGE and run at 80V for 45 min. Each sample lane was excised separately, cut into small pieces (approximately 1 mm2 pieces) and washed with 75% acetonitrile (ACN) containing triethylammonium bicarbonate (TEAB, 25 mM). The gel pieces were reduced with Tris 2- carboxyethyl phosphine hydrochloride (5 mM) and then alkylated with methyl methanethiosulfonate (10 mM). Gel pieces were dehydrated using ACN and subjected to protein digestion with sequencing grade modified trypsin (Promega, Madison, WI) at 37°C. The peptides were extracted using 50% acetonitrile, 5% acetic acid and concentrated using vacuum concentrators (Eppendorf AG, Hamburg, Germany).PrideiTRAQdeamidated residueAcquired data was further processed using Proteome Discoverer (PD) v1.4 (Thermo Scientific, San Jose, USA) with deisotope in MS/MS. The raw files were directly imported into the PD and further processed using designed workflow.Database search was performed against the UniProt human database.ProteomicsProf Sze S KQ ExactiveNanyang Technological University, SingaporePARTIALHomo Sapiens (human)30691479 Adav SS, Park JE, Sze SK. Quantitative profiling brain proteomes revealed mitochondrial dysfunction in Alzheimer's disease. Mol Brain. 2019 12(1):8 10.1186/s13041-019-0430-yssadav@ntu.edu.sgNanyang Technological UniversitySingaporeMitochondrial dysfunction is a key feature in both aging and neurodegenerative diseases including Alzheimer's disease (AD), but the molecular signature that distinguishes pathological changes in the AD from healthy aging in the brain mitochondria remain poorly understood. In order to unveil AD specific mitochondrial dysfunctions, this study adopted a discovery-driven approach with isobaric tag for relative and absolute quantitation (iTRAQ) and label-free quantitative proteomics, and profiled the mitochondrial proteomes in human brain tissues of healthy and AD individuals. LC-MS/MS-based iTRAQ quantitative proteomics approach revealed differentially altered mitochondriomes that distinguished the AD's pathophysiology-induced from aging-associated changes. Our results showed that dysregulated mitochondrial complexes including electron transport chain (ETC) and ATP-synthase are the potential driver for pathology of the AD. The iTRAQ results were cross-validated with independent label-free quantitative proteomics experiments to confirm that the subunit of electron transport chain complex I, particularly NDUFA4 and NDUFA9 were altered in AD patients, suggesting destabilization of the junction between membrane and matrix arms of mitochondrial complex I impacted the mitochondrial functions in the AD. iTRAQ quantitative proteomics of brain mitochondriomes revealed disparity in healthy aging and age-dependent AD.Quantitative profiling brain proteomes revealed mitochondrial dysfunction in Alzheimer's disease.Adav Sunil S SS, Park Jung Eun JE, Sze Siu Kwan SK, Sze Siu Kwan SKthe brain, liquid chromatography tandem mass spectroscopy, Presenile Alzheimer Dementia, ALZHEIMERS DIS, human being, 1010001N11Rik, Peptidomics, Early Onset, number, Neurologic Diseases, Degenerative Neurologic Disorders, Neurologic Degenerative Condition, Aging, IB, Focal Onset, Mitochondrial Contractions, presence, rhabdomyosarcoma, Alzheimer's disease, unspecified (disorder), LC-MS-MS, Neurodegenerative Diseases, ALZHEIMER DIS, AD, SDR22E1, unspecified, alveolar childhood rhabdomyosarcoma, [X]Dementia in Alzheimer's disease, Neurologic Disorders, Biological, integral component of membrane, ATP-synbeta, LC-MSMS, Mitochondrion, synganglion, cytopathology, NDUFS2L, MLRQ, Nervous System Degenerative Diseases, Senescence, study, Nervous System, LATE ONSET ALZHEIMER DIS, Degenerative Condition, LCMSMS, DAT - Dementia Alzheimer's type, DmelCG11154, Healthy Ageing, NADH:plastoquinone reductase complex, CI39k, Contraction, dysfunction, beta-ATPase, membrane region, Tissue, CI-MLRQ, suprasegmental levels of nervous system, Neurodegenerative Disorder, man, Neurodegenerative Disorders, free, Well Aging, FOCAL ONSET ALZHEIMERS DIS, Biological Aging, Neurologic, ATPsyn b, Ageing, Neurologic Degenerative Diseases, NADH dehydrogenase complex (quinone), Degenerative Neurologic Disease, ATPasebeta, AD - Alzheimer's disease, Complex I, rhabdomyosarcoma type 2, Alzheimer Disease, ATPase beta, Clients, Alzheimer Type Dementia, Pathologies, Degenerative Neurologic Diseases, breakpoint, Neurologic Degenerative Disease, region of membrane, Spinal Cord, ALZHEIMER DIS EARLY ONSET, Alzheimer's disease (disorder), Presenile, associated, Alzheimers Dementia, alveolar, ATPB, Alzheimers disease, somatic mutation, ATP, LC-MS2, junction, Alzheimer Senile Dementia, ATPsyn-&bgr, Senile, membrane, Disease, Neurologic Disorder, suprasegmental structures, ATPsyn-b, ARMS, Healthy., Acute Confusional Senile Dementia, LC-MS/MS, integral to membrane, Aging Well, membranous organ component, pediatric alveolar rhabdomyosarcoma, encephalon, Client, RMS2, Alzheimer's Dementia, results, Primary Senile Degenerative Dementia, Degenerative Neurologic Disorder, [X]Dementia in Alzheimer's disease (disorder), Alzheimer Type, ATP-syn-B, rhabdomyosarcoma alveolar, Contractions, count in organism, LC/MS/MS, ML-1, NADH dehydrogenase complex (plastoquinone), anatomical junction, rhabdomyosarcoma 2, CI-39k, whole membrane, NOS, Amplification Refractory Mutation System, arms, plastid NADH dehydrogenase complex (plastoquinone), Dementia, CG11154, boundary, Degenerative Conditions, Mitochondrial, transmembrane, Alzheimers, membrane of organ, Well, histopathology, Degenerative Diseases, CI-9k, Dementia in Alzheimer's disease, Alzheimer, Encephalon, Alzheimer's Disease Pathway, Dementias, Neurologic Degenerative Conditions, pathophysiology, CC6, Neurologic Disease, Alzheimer Dementia, human, Healthy, Ageing Well, Mitochondrial Contraction, Mitochondrial dysfunction, mitochondria, Senile Dementia, Late Onset, Patient, Degenerative, liquid chromatography-tandem mass spectroscopy, ATPIB, Dementia in Alzheimer's disease (disorder), paediatric alveolar rhabdomyosarcoma, monomorphous round cell rhabdomyosarcoma, alveolar rhabdomyosarcoma (morphologic abnormality), Neurodegenerative Disease, liquid chromatography tandem mass spectrometry, Central Nervous System, Alzheimer's Disease, alveolar rhabdomyosarcoma, quantitative, alveolar rhabdomyosarcoma (disease), biopsy, NADH dehydrogenase complex (ubiquinone), Proteomes, Dementia of the Alzheimer's type, presence or absence in organismSan, SAN, Svc, data, Bru, 2810441M03Rik, nat5, Col4a-1, human being, Raw, NAT13, mak3, atado, NAT5P, CG12352, Data Base., NAT13P, Nat13, man, not genetically inherited, Thermo Scientific, human, hNAT5, san, AW112078, Workflows, hSAN, DmelCG12352, Nat5, NAT5, Del(8)44H, Mak3, nat13, Work Flow, 2600005K24Rik, DmAAF34715, Work Flows, Data Base, Mak3p, MAK3, spanthe brain, Presenile Alzheimer Dementia, Senile, Alzheimer disease, suprasegmental structures, Alzheimers Diseases, Peptidomics, Early Onset, Alzheimer Syndrome, Acute Confusional Senile Dementia, Sclerosis, familial, total expressed protein, Alzheimer disease 1, function, Early Onset Alzheimer Disease, Focal Onset, encephalon, Primary Senile Degenerative Dementia, Alzheimer Type, Primary Senile Degenerative, Alzheimer Dementias, AD, Alzheimer's Diseases, 1, synganglion, with cerebral amyloid angiopathy, Dementia, presenile and senile dementia, Familial Alzheimer Disease (FAD), Alzheimer Diseases, early-onset, Alzheimer, Encephalon, susceptibility to, Alzheimer Type Senile Dementia, suprasegmental levels of nervous system, Focal Onset Alzheimer's Disease, Alzheimer-Type (ATD), Late Onset Alzheimer Disease, Alzheimer Dementia, late-onset, Alzheimer Sclerosis, Presenile Dementia, Senile Dementia, Late Onset, Alzheimer Type Dementia (ATD)., Alzheimer Disease, Familial (FAD), Alzheimer Type Dementia, AD1, early-onset familial form of Alzheimer disease, Acute Confusional, Alzheimer-Type Dementia (ATD), protection against, Alzheimer's Disease, Presenile, Familial Alzheimer Diseases (FAD), Proteomesthe brain, Alzheimer Senile Dementia, Presenile Alzheimer Dementia, Senile, Disease, suprasegmental structures, ALZHEIMERS DIS, Early Onset, Acute Confusional Senile Dementia, number, Focal Onset, Dementia of the Alzheimer's type., presence, encephalon, Alzheimer's disease, Alzheimer's Dementia, unspecified (disorder), Primary Senile Degenerative Dementia, [X]Dementia in Alzheimer's disease (disorder), Alzheimer Type, ALZHEIMER DIS, AD, count in organism, unspecified, [X]Dementia in Alzheimer's disease, NOS, synganglion, Dementia, LATE ONSET ALZHEIMER DIS, Alzheimers, DAT - Dementia Alzheimer's type, Dementia in Alzheimer's disease, Alzheimer, Encephalon, Alzheimer's Disease Pathway, Dementias, suprasegmental levels of nervous system, Alzheimer Dementia, FOCAL ONSET ALZHEIMERS DIS, Mitochondrial dysfunction, Senile Dementia, Late Onset, AD - Alzheimer's disease, Alzheimer Disease, Alzheimer Type Dementia, Dementia in Alzheimer's disease (disorder), ALZHEIMER DIS EARLY ONSET, Alzheimer's Disease, Alzheimer's disease (disorder), quantitative, Presenile, Alzheimers Dementia, Proteomes, Alzheimers disease, presence or absence in organismIL1BC, MeCN, NCMe, ectodin, Vinegar, CASP-1, ethanoate, CG7788, crice, Essigsaeure, SDH, Basodexan, Hydrogenchlorid, tissue specimen, CG11121, dmTAF[[II]]230, 2-Propanone, peptide, SDS, Cut, Polypeptides, old, hydrogen chloride, E260, peptido, BANF, Glacial Acetic Acid, l(1)7Ba, l(1)7Bb, CH3-C#N, Urea, 2, Min, synganglion, Il1bc, Fs(3)Hor, present in fewer numbers in organism, MMTS, DmelCG42273, DL-Asparagine, portion of tissue, DmelCG2684, asparagina, C79325, reference sample, TFIID TAF250, peptides, asparagine, cel, E927b, N, L-Asparagine, 2610036I19Rik, Tissue, 2610510L13Rik, hypoplasia, Acetic Acid, min, USAG-1, Age of onset, mAPC, proteins, suprasegmental levels of nervous system, NTef2, Acetic Acid Glacial, SO, ASN, Protein Degradation, IL-1BC, Asn, CG11387, CH3-COO(-), AI047805, fSAP152, Wasserstoffchlorid, decreased, dehydrated, SOLO DANCERS, ICE, ACN, sample, Acn, MeCO2H, methyl methanesulfonothioate, CT, ethoic acid, TEAB, So, 0610006G05Rik, dTAF[[II]]230, suprasegmental structures, Degradations, Caspase-1 subunit p10, ice, iCE, drice, ACETATE ION, Ct, TAF200, Dmel_CG7826, AI836084, MM2, TAFII-250, TAF250/230, ur, Fs(3)Sz11, DmelCG7788, carbamide, TAFII250, Glacial, Dm1, drIce, drICE, Digestion, precocious, Chlorwasserstoff, tissue portion, simple tissue, BcDNA:GH10590, Ethanoat, Dmel_CG7835, Acetic acid, Mnb, MNB, Vacuums., Ethylic acid, Encephalon, Protein Digestions, P45, HCl, RGAG2, pooled, methyl methanethiolsulfonate, 2-amino-3-carbamoylpropanoic acid, AW124434, CG17603, TAF[[II]], beta Trypsin, early, H2NC(O)NH2, Patient, Taf250, Sostl, Horka, SR3-5, Wise, Drice, p45, CG2684, Fs(3)Horka, Polypeptide, methyl cyanide, chlorane, DRICE, 1728, TAF230, Gruppe, the brain, F10B6_15, advanced, d230, E-260, l(1)VE614, chlorure d'hydrogene, DrIce, DrICE, Degradation, Hasp, Gene, CH3-COOH, dTAFII250, Carbamide, ACINUS, EfW1, CG7826, F10B6.15, MA2, Buffer, Karbamid, Methanecarboxylic acid, reduced, DmelCG11121, Azetat, dmTAF1, Taf230, subnumerary, Harnstoff, CG7835, Gene Products, CG42273, DmF2, tiny, Carmol, PH3, cloruro de hidrogeno, CH3CO2H, Pro-Mega, TAF250, lod, Taf200, somda, dTAF[[II]]250, Acinus, Hydrogen chloride, cell, acetate, PCE-2, beta-Trypsin, phosphane, 4733401P19Rik, Taf1p, decreased number, Protein Degradations, kf, acinusL, Asparagin, dTAF250, Table, DmelCG11387, Caspase-1 subunit p20, acinusS, grupos, Clients, peptidos, TAF, Controlled, Drl, small, Controlling, DYRK1, AcOH, TAF[[II]]250, grupo, 1-(14)C-labeled, 3H-labeled, caspase 3, Proteins, ion(1-), l(3)84Ab, BG:DS00004.13, chloridohydrogen, CE-2, acetonitrile, Protein Digestion, buffer, encephalon, Client, Digestions, Cell, mKIAA0670, Peptide, group, Mdu, dTAF230, polypeptide, [HCl], HOAc, Proteolyses, carbonyldiamide, dry, mda, p230, Protein, Hydrochloride, TAF[[II]]250/230, TFIID, Dyrk1, CES2A1, ACETONITRILE, ami, cyanomethane, Taf[[II]]250, AU020952, acetic acid ammonium salt, TAF[[II]]230, underdeveloped, E 260, uree, med, urea, CC1, Rest, Tripcellim, SWDS, hydrogen phosphorus, IL-1 beta-converting enzyme, patient, TAF[II]250, acide acetique, ethanenitrile, Interleukin-1 beta-converting enzyme, Age symptoms begin, CGI-97, Lds, 4-diamino-4-oxobutanoic acid, sample population, UREA, ME-IV, Interleukin-1 beta convertase, Protein Gene Products, incised, Gene Proteins, Trypure, DmelCG17603, hydrogen phosphide, MeCOOH, ACETIC ACID, 3.4.22.36, MeCO2 anion, Peptid, INS No. 260, acetic acid, SCH, groupe, hydrochloric acid, Ethanoic acid, TAF1the brain, count in organism, suprasegmental structures, human being, Peptidomics, Tissue., Encephalon, number, total expressed protein, synganglion, quantitative, suprasegmental levels of nervous system, Proteomes, man, free, presence, encephalon, human, presence or absence in organism2391trueProteomics of Brain Proteome Revealed Altered Mitochondrial Function in Alzheimer DiseaseA discovery-driven approach with isobaric tag for relative and absolute quantitation (iTRAQ) and label-free quantitative proteomics was used to profiled the mitochondrial proteome in human brain tissues of healthy and AD individuals.2019-02-012018-12-31PXD012203445446415249917559311738804333092866432359839062887053271602461962461971603293581136358945327583851187947572307135122511775058555714683536492158910306291592915836415158493885803327159100226388869151355888704351464796928771332803836545833398580894621182590632957174934124727256322732192867281395451329491408169180454139036345301143114098108713554771424507326443555127443271469455972937514615754647842242208964139231744712701390114319338293550823074111481194669489693529372512646907275802402165993665812165952941281283296543128212803395232181843183292043531522811257554787575930797253623114367331159556444214321381849222426191454811096976226155153111795733472059687986588845586265281736309431796989361604885664162425678253175136303555432046565050632633NCBITaxon:13134565860688607699389427955453512014887795921612941002642032890969456967631076228531643518543121574577760494144242324113NCBITaxon:177392979310239101178709NCBITaxon:4055974990799136526112273498217170187367451011656915693132842610360983341336795663303NCBITaxon:4932992588391000589873299404458611535722491134305311563120175544219329935872631787236669872464268727421575476242231414611510416079130554689111800661255228562136162997679825102169982311746731167610807723264244468941536776744685960039376511822635735784588086363266689NCBITaxon:26970491031298382413681089319975961231974794652283291761966277668960596061572951372211711012567371233435105231100904054998638783104298635788401937334961550877119821597397574878229719721519089850764802563184189856239190264946454635286746360NCBITaxon:110712883574612874601134506649125314594352638NCBITaxon:615797787237953440812633803945264114595361235178616722724323074691123869978540979541NCBITaxon:2954424327762791292497036125180284812426428150475269796102993886599034694173862634751541554036329979662877323962899548657558462823823522862871736231399463601068842043601043994796858355847954440426071016780781440772NCBITaxon:61918402317199312811836100361050231855791908021878783749907038476641692259634591065922607046183260705334542260707NCBITaxon:780NCBITaxon:15024515168853187029211586910371647209285747078124966842528619212638541094343197383379192875NCBITaxon:10359282912680639560295987044830064180224275210555242354432243081433614690081502575412983964271191364516996328104121697927262327262430085212389936436801097791356223347471821314269704958331361858030826882976052779638185833424090611477871274414153681639588858130767494022432640817212816140559204254687613837081274423285099011912744201274426519534911370249240543734131641660817562615282352567506028532189517731193501846451450511492412153239564818822970915800257125614801549031384736031423166385962859631015101450520493227591428693732664179332648373153NCBITaxon:961529722109767711211144937608333419110792762833322375612666255559292484791486917749200360094340731203258352472259447517503754516499085151514389923747306914790000-0002-8559-4885