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DuongNot availableBrainBrain Tissue Homogenization and Protein Digestion---Procedures for tissue homogenization were performed essentially as described23. In total, 40 samples across four pathological groups (n=10 per control, PD, AD and AD/PD groupings) were collected from both brain regions (frontal cortex and anterior cingulate); 31 of these cases had matched tissues across brain regions (Data citation 1). Approximately 100mg (wet tissue weight) of brain tissue was homogenize in 8 M urea lysis buffer (8 M urea, 100 mM NaHPO4, pH 8.5) with HALT protease and phosphatase inhibitor cocktail (ThermoFisher, Cat# 78440) using a Bullet Blender. Each sample tube (Rino, NextAdvance) was supplemented with ~100 µL of stainless steel beads (0.9 to 2.0 mm blend, NextAdvance) and 500 µL of lysis buffer. Tissues were added immediately after excision and samples were then placed into the bullet blender (in 4°C cold room). The samples were homogenized for 2 full 5 min cycles and the lysates were transferred to new Eppendorf Lobind tubes. Each sample was then sonicated for 3 cycles consisting of 5 seconds of active sonication at 30% amplitude followed by 15 seconds on ice. Samples were then centrifuged for 5 minutes at 15000 g and the supernatant was transferred to a new tube. Protein concentration was then determined by bicinchoninic acid (BCA) assay (Pierce). Prior to further processing, protein integrity and concentration accuracy was assessed by 1 dimensional SDS-PAGE (Supplementary Figure 1). For protein digestion, 100 µg of each sample was aliquoted and balanced with additional lysis buffer. Samples were reduced with 1mM dithiothreitol (DTT) at room temperature for 30 min, followed by 5 mM iodoacetamide (IAA) alkylation in dark for another 30 min. Samples were then diluted 8 folds with 50 mM triethylammonium bicarbonate (TEAB). Lysyl endopeptidase (Wako) at 1:100 (w/w) was added and digestion was allowed to proceed overnight. Trypsin (Promega) was then added at 1:50 (w/w) and digestion was carried out for another 12 hours. The peptide solution was then acidified to a final concentration of 1% formic acid (FA) and 0.1% triflouroacetic acid (TFA) and desalted with a Sep-Pak C18 column (Water). Each Sep-Pak column was activated with 1 mL of methanol, washed with 1 mL of 80% acetonitrile, and equilibrated with 2 x 1 mL 0.1 % TFA. The samples were then loaded and each column was washed with 2 x 1 mL 0.1% TFA. Elution was performed with 2 - 400 µL rounds of 50% acetonitrile. Tandem mass tag (TMT) peptide labeling ---- An aliquot equivalent to 20 µg was taken from each sample and combined to make a global internal standard (GIS) per brain region. All peptides mixtures were dried down using a speedVac. For each tissue region, 5 batches of 10-plex TMT kits (ThermoFisher, Cat# 90111) were used to label the 40 samples and 10 GIS mixtures. Samples arrangement were shown in Supplementary Tables 1 and 2. In each batch, 2 GIS mixtures were labeled with TMT channels 126 and 131 while the 8 middle TMT channels were used to label 2 samples from each disease state. Labeling was performed according to manufacturer’s protocol. Briefly, each sample (80 µg of peptides each) was resuspended in 100 µL of 100 mM TEAB buffer. The TMT labeling reagents were allowed to equilibrate to room temperature and 41 µL anhydrous acetonitrile was added to each reagent channel and softly vortexed for 5 minutes. Peptide suspensions were transferred to corresponding TMT channel reagent and incubated 1h at room temperature. The reaction was quenched with 8 ul of 5% hydroxylamine. To ensure complete labeling select channels from each batch were analyzed by LC-MS/MS according to previously published methods38. All 10 channels were then combined and the mixture was dried by vacuum to ~ 500 µL. Sep-Pak desalting was performed and the elution was dried to completeness. ERLIC offline fractionation ---- Dried samples were resuspended in 100 µL of ERLIC buffer A (90% acetonitrile with 0.1% acetic acid) and loaded onto a PolyWAX LP column (20 cm by 3.2 mm packed with 300Å 5 µm beads (PolyLC Inc) as reported previously34. An Agilent 1100 HPLC system consisting of a degasser, a binary pump, an autosampler, a microflow UV detector, and a fraction collector was used to carry out the fractionation. The gradient was from 0 to 50% ERLIC buffer B (30% ACN with 0.1% FA) over 45 minutes. A total of 44 fractions were collected and then combined to a total of 21 fractions. Fractions 1 to 20 consisted of alternating combinations (1 and 21, 2 and 22, etc.) and fraction 21 consisted of the last fractions (41 to 44).PrideNicholas SeyfriedOrbitrap FusionEmory University School of Medicine Biochemistry DepartmentPARTIAL29533394 Ping L, Duong DM, Yin L, Gearing M, Lah JJ, Levey AI, Seyfried NT. Global quantitative analysis of the human brain proteome in Alzheimer's and Parkinson's Disease. Sci Data. 2018 5:180036 10.1038/sdata.2018.36Center of Neurodegenerative Diseasesnseyfri@emory.eduMass SpectrometryShotgun proteomicsParkinson's DiseaseAlzheimer's DiseaseHumanBrainParkinson'sSpsLc-ms/msTmtAlzheimer'shttp://www.ebi.ac.uk/pride/archive/projects/PXD007160TMTiodoacetamide derivatized residuemonohydroxylated residuedeamidated residueProtein Identification and Quantification---- Raw data files from Orbitrap Fusion were processed using Proteome Discover (version 2.1). MS/MS spectra were searched against the UniProt Human proteome database (90,300 total sequences). The respective FASTA database is deposited in the on the Synapse web portal (see data records). Sequest parameters were specified as: trypsin enzyme, two missed cleavages allowed, minimum peptide length of 6, TMT tags on lysine residues and peptide N-termini (+ 229.162932 Da) and carbamidomethylation of cysteine residues (+ 57.02146 Da) as fixed modifications, oxidation of methionine residues (+ 15.99492 Da) and deamidation of asparagine and glutamine (+0.984 Da) as a variable modification, precursor mass tolerance of 20 ppm, and a fragment mass tolerance of 0.6 daltons. Peptide spectral match error rates were determined using the target-decoy strategy coupled to Percolator modeling of true and false matches. Reporter ions were quantified from MS3 scans using an integration tolerance of 20 ppm with the most confident centroid setting. An MS2 spectral assignment false discovery rate (FDR) of less than 1% was achieved by applying the target-decoy strategy. Following spectral assignment, peptides were assembled into proteins and proteins and were further filtered based on the combined probabilities of their constituent peptides to a final FDR of 1%. In cases of redundancy, shared peptides were assigned to the protein sequence with the most matching peptides, thus adhering to principles of parsimony.ProteomicsHomo Sapiens (human)dduong@emory.eduBiologicalBiomedicalUnited StatesPatients with Alzheimer's disease (AD) and Parkinson's disease (PD) often have overlap in clinical presentation and brain neuropathology suggesting that these two diseases share common underlying mechanisms. Currently, the molecular pathways linking AD and PD are incompletely understood. Utilizing Tandem Mass Tag (TMT) isobaric labeling and synchronous precursor selection-based MS3 (SPS-MS3) mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11 840 protein groups representing 10 230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra- and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of disease-specific protein signatures and molecular pathways that are common in AD and PD.Global quantitative analysis of the human brain proteome in Alzheimer's and Parkinson's Disease.Ping Lingyan L, Duong Duc M DM, Yin Luming L, Gearing Marla M, Lah James J JJ, Levey Allan I AI, Seyfried Nicholas T NTsodium salt, extent, ammonium formate, 13C-labeled, IL1BC, cadmium salt, MeCN, PLXN5, Vinegar, CASP-1, chronic obstructive pulmonary disease (COPD), SDH, Basodexan, 2-(indol-3-yl)ethanoic acid, magnesium formate, Apaf-1, Steels, zinc salt, Lobus Frontalis, SeP, Bca, SDS, Polypeptides, protein polypeptide chains, CEH, E260, domestic cat, T22F8_160, cobalt(II) formate dihydrate, ATGPR7, CH3-C#N, Chronic irreversible airway obstruction, Urea, 1, GRP8, 2, NEPII, GRP7, AGM4, SEH, Frontal, Il1bc, 2210418N07, bacterial catalase-peroxidase activity, WMS, Sep, SEP, (R*, bca, C79325, hac-1, CT21282, weight-weight percentage, Tissue, CAFL - Chronic airflow limitation, proteins, suprasegmental levels of nervous system, lobus frontalis, Acetic Acid Glacial, IL-1BC, HPLC, sEP, AI047805, Stainless Steels, haem catalase activity, decreased, column, disease (COPD), anatomical tube, scientific observation, ACN, sample, Acn, MeCO2H, Homo sapiens disease, autolysin activity, Stainless steel, phosphatase, nickel salt, SGS, AI315345, LC-MS2, Brodmann's, equilase activity, chronic obstructive lung disease [Ambiguous], suprasegmental structures, Degradations, Caspase-1 subunit p10, cobalt (+2) salt, completeness, acid, anon-53Fa, l(2)SH0173, Frontal Eye Fields, A330009E03Rik, DmelCG7788, ACMICD, CHRONIC OBSTRUCTIVE AIRWAY DIS, (Indol-3-yl)acetate, sodium (4:1:1) salt, Glacial, Dm1, magnesium salt, simple tissue, Airflow Obstruction, CG6829, Hydrogen Oxide, dark/hac-1/dapaf-1, ACGNAT, GLYCINE-RICH PROTEIN 8, Chronic Obstructive Airways Disease, Acid, Chronic obstructive lung disease, frontal region, Ethylic acid, LY57, Protein Digestions, formate, cromium (+3), reagent, Supplementary, study protocol, beta Trypsin, w/w, Indole-3-acetic acid, Area 8, heteroauxin, F2G1.4, Supplementary Eye Fields, OBSTRUCTIVE PULMONARY DISEASE (COPD), spirit of wood, liquid chromatography-tandem mass spectroscopy, duct, Drice, bacteriolytic toxin activity, ammonium (4:1) salt, methyl cyanide, DROCATHPO, DRICE, lead (+2) salt, TMT, bs36h11.y1, cortex of frontal lobe, Methyl Alcohol, Cleland Reagent, Hydroxylamine Hydrochloride, mKIAA0670., Lobe, F10B6_15, nickel formate dihydrate, lead formate, region or site annotation, DrIce, DrICE, aluminum salt, CAO - Chronic airflow obstruction, Pierce, tables, 4-dimercapto-, Carbamide, CH3OH, CHRONIC OBSTRUCTIVE PULM DIS, Chronic obstructive pulmonary disease NOS, R*)-, protein-containing complex, body system, and RNA binding 1, CG7826, F10B6.15, Chronic obstructive pulmonary disease finding, CrAT, PULMONARY DISEASE (COPD), manganese catalase activity, Ly57, lobi frontales, LC-MSMS, Brodmann's Area 8, CG7835, CG42273, disease or disorder, system, Carmol, positional, anatomical systems, 2310061K05Rik, Acinus, thallium (+1) salt, PCE-2, beta-Trypsin, rubidium salt, frontal cortex, Frontal Eye Field, 4733401P19Rik, methanoic acid, study assay, Solution, acinusL, DmelCG6871, Sep-Pak C18, ATGRP7, Caspase-1 subunit p20, acinusS, ATGRP8, Steel, NEC, Chronic, peptidos, collection tube, Saeure, Supplementary Eye Field, inhibitors, measuring, 1H-indol-3-ylacetic acid, dark/dapaf-1/hac-1, AcOH, DMCATHPO, mass percentage, heme catalase activity, 1-(14)C-labeled, chronic obstructive airways disease NOS, caspase 3, dApaf-1, COAD, disorders, Clelands Reagent, Mell1, Methyl alcohol, potassium formate, CE-2, copper (+2) salt, Mischung, COLD - Chronic obstructive lung disease, acetonitrile, buffer, encephalon, Digestions, chronic, polypeptide, APAF1, Cortex, Temperatures, native protein, Proteolyses, carbonyldiamide, Hac-1, Felis domesticus, cupric formate, condition, MFS1, Sodium, MeOH, (COPD), chronic airway obstruction, chronic obstructive, aluminum formate, dJ142L7.2, CAL - Chronic airflow limitation, CS1, Cleland's, Achromobacter protease I, AU020952, lithium formate, holin, underdeveloped, Saeuren, GR-RBP7, GR-RBP8, 3-Indolylessigsaeure, SWDS, Dark/Dapaf-1/HAC1, CG6871, IL-1 beta-converting enzyme, ethanenitrile, Interleukin-1 beta-converting enzyme, primary structure of sequence macromolecule, ME-IV, achromopeptidase, plan specification, Cleland's Reagent, Eye Fields, MeCOOH, ACETIC ACID, chronic obstructive lung disease (disorder), liquid chromatography tandem mass spectrometry, NEP2, Methoxide, Ethanoic acid, chronic obstructive pulmonary disease, liquid chromatography tandem mass spectroscopy, Hac-1/Dark, T22F8.160, NCMe, and rna binding 2, Chronic Airflow Obstructions, DmelCG6829, zinc formate, Nl1, CG7788, Cs-1, crice, lead salt, Essigsaeure, protein, lysis, Alkylations, peptide, ammonium tetraformate, IAA, ClvPrd, peptido, diseases, Glacial Acetic Acid, BANF, chronic obstructive airways disease NOS (disorder), NL1, Min, diseases and disorders, synganglion, Apaf1, NL2, Chronic Obstructive Pulmonary Disease (COPD), protein aggregate, present in fewer numbers in organism, ARK, DmelCG42273, wood alcohol, portion of tissue, human disease, Frontal Cortex, COLD (chronic obstructive lung disease), LCMSMS, reference sample, peptides, dermoid cyst with malignant transformation, NEC in ICD9CM_2006, E927b, 2610036I19Rik, 2610510L13Rik, hypoplasia, Acetic Acid, min, arc, mAPC, achromobacter beta-lytic protease (blp), copper, ark, Protein Degradation, Frontal Cortices, T1, Chronic airflow limitation, Brodmann Area 8, reaction, Hydroxylammonium Chloride, fSAP152, lithium salt, SOLO DANCERS, Sputolysin, GLYCINE RICH PROTEIN 7, ICE, ethoic acid, necrosis, Lyw-57, dApaf1, TEAB, Sodium Methoxide, glycine-rich RNA-binding protein 8, GPHYSD2, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ammonium (2:1) salt, reagents, catalase-peroxidase activity, CHRONIC, Tube, obstructive lung disease, Alcohol, ice, iCE, D-Apaf-1, drice, sample tube, LC-MS/MS, Dmel_CG7826, AI836084, 2.3.1.7, regio frontalis, ur, Airflow Obstructions, AI195249, pulmonary disease (COPD), TUBE, SLP65, any method, carbamide, Ly-57, S-adenosyl-L-methionine:thiol S-methyltransferase activity, catalase reaction, batch, weight, Cleland, MMEL2, Digestion, frontal lobe cortex, drIce, drICE, low temperature, CHRONIC OBSTRUCTIVE, chronic obstructive pulmonary disease and allied conditions, Diseases, lysyl endoprotease, tissue portion, Chronic airway disease, bacteriocin activity, NOS, IES, nickel (+2) salt, reactif, Carbinol, GAT, Dmel_CG7835, region, Acetic acid, COPD NOS, carbinol, CHRONIC OBSTRUCTIVE LUNG DIS, Mnb, MNB, Chronic airway obstruction, SLP-65, ammonium salt, positional polypeptide feature, cold, BASH, Xylella fastidiosa str. Temecula1, acide, Sonications, Encephalon, P45, Brodmanns Area 8, hydrogen-peroxide:hydrogen-peroxide oxidoreductase activity, cobaltous formate, frontal neocortex, acids, 3-Butanediol, hac1, acido, MASS, AW124434, Felis silvestris catus, Stainless, organ system, dapaf-1S, Chronic Airflow Obstruction, METHANOL, disease, H2NC(O)NH2, Wood, apaf-1, lysin activity, dapaf-1L, COPD - Chronic obstructive pulmonary disease, Acetamide, copper salt, chronic obstructive airways disease, p45, Eph2, Polypeptide, obstructive pulmonary disease (COPD), 1728, U00145, COLD, chronic obstructive lung disease, gray matter of frontal lobe, the brain, Cas1, other disease, Carnitine acetylase, E-260, Dapaf-1/HAC-1, DISEASE (COPD), Reagent, Degradation, cesium salt, FBN, CH3-COOH, PLEXIN-B1, Methyl, circadian rhythm, ACINUS, Methylalkohol, LC-MS-MS, Buffer, formic acid, Dark/Hac-1/dApaf1, Karbamid, Cold, method, Methanecarboxylic acid, Hac1, potassium salt, Dark/Hac-1/dApaf-1, Pulmonary Disease, polypeptide chain, reduced, subnumerary, ECTOL1, 14C-labeled, method used in an experiment, Harnstoff, Wood Alcohol, caperase activity, tiny, CH3CO2H, Pro-Mega, Cold Temperatures, CG2916, reactivo, dapaf-1, inhibiteur, CatA, CATA, Indoleacetic acid, dapaf, labeling, Eye Field, dark, methanol, decreased number, calcium formate, Protein Degradations, Chronic Obstructive, Xylella fastidiosa (strain Temecula1 / ATCC 700964), OCTD, non-neoplastic, Table, inhibidor, (indol-3-yl)acetic acid, Catl, DARK, Suspension, wood naphtha, SELP, site, disorder, cats, cromium (+3) salt, dArk, Dapaf-1, 2-iodo-, sodium formate, thiol methyltransferase activity, Controlled, BLNK-S, COPD, small, Controlling, data, COAD - Chronic obstructive airways disease, DYRK1, nickel formate, 3H-labeled, protein complex, not elsewhere classified, strontium formate, inhibitor, apaf1, medical condition, Protein Digestion, strontium salt, Carnitine acetyltransferase, PULM DIS CHRONIC OBSTRUCTIVE, Peptide, Chronic obstructive pulmonary disease finding (finding), Methanol, sep5, LC/MS/MS, HOAc, natural protein, Brodmann, Protein, AI551343, sequence, Dyrk1, GLYCINE-RICH RNA-BINDING PROTEIN 7, CES2A1, Dark, Vacuums, CAT, connected anatomical system, grey matter of frontal lobe, Dark/Apaf-I, ACETONITRILE, cyanomethane, WMS2, teratoma with malignant transformation, optidase activity, chronic obstructive airway disease, Temperature, Cas-1, E 260, uree, Dops, urea, CC1, DmelCG2916, Tripcellim, phosphoric monoester hydrolase activity, acide acetique, cat, CGI-97, dApaf-1/DARK/HAC-1, sample population, chromic formate, UREA, Interleukin-1 beta convertase, Trypure, Cat01, concentration, wood spirit, SSKS, 3.4.22.36, calcium salt, cold (chronic obstructive lung disease), Peptid, INS No. 260, Chronic Obstructive Lung Disease, acetic acid, SCH, Frontal Lobes, dAPAF-1the brain, Parkinson's syndrome, Presenile Alzheimer Dementia, Parkinson's disease, Parkinsons, Disease, Alzheimer disease, suprasegmental structures, ALZHEIMERS DIS, human being, sporadic Alzheimer's disease, determination, Parkinson's disease NOS, number, familial, total expressed protein, presence, encephalon, Alzheimer's disease, Alzheimer's Dementia, Alzheimer dementia, unspecified (disorder), Alzheimer Type, [X]Dementia in Alzheimer's disease (disorder), ALZHEIMER DIS, AD, count in organism, [X]Dementia in Alzheimer's disease, chemical analysis, NOS, synganglion, Idiopathic PD., Dementia, Presenile Alzheimer, presenile and senile dementia, Alzheimers, Parkinson disease, DAT - Dementia Alzheimer's type, Parkinson's disease (disorder), Dementia in Alzheimer's disease, Alzheimer, Encephalon, Alzheimer's dementia, suprasegmental levels of nervous system, man, Alzheimer Dementia, human, Alzheimer's, Parkinsonian disorder, Parkinson's disease NOS (disorder), AD - Alzheimer's disease, paralysis agitans, Alzheimer Disease, Alzheimer Type Dementia, Dementia in Alzheimer's disease (disorder), Parkinson syndrome, assay, Alzheimer's disease (disorder), quantitative, Presenile, Alzheimers Dementia, Proteomes, Alzheimers disease, presence or absence in organism, Dementia of the Alzheimer's type, Alzheimers dementiaBru, GLUTAMINE, human being, Cysteine Hydrochloride, 2-amino-4-(methylsulfanyl)butanoic acid, Raw, ion, Lysine Hydrochloride, False, 5-diamino-5-oxopentanoic acid, L Isomer, Levoglutamide, FBN, Hasp, Gene, protein, precursor, (2S)-2-amino-4-carbamoylbutanoic acid, protein-containing complex, L-(+)-glutamine, peptide, Polypeptides, protein polypeptide chains, Personal, L-Isomer Methionine, Lysine Acetate, L-glutamine, Methionine, L-Glutaminsaeure-5-amid, Drug Tolerance, ClvPrd, peptido, polypeptide chain, ECTOL1, Gene Products, L-Methionine, Synapse, 2, L-2-aminoglutaramic acid, Del(8)44H, Lysine, Half-Cystine, Documents, protein aggregate, Pedameth, WMS, L Lysine, Svc, DL-Asparagine, proportion, asparagina, F, peptides, dermoid cyst with malignant transformation, asparagine, K, MS3, L Cysteine, M, (2S)-2, iones, MS2, N, L-Asparagine, D-Glutamine, beta-Trypsin, Q, E430039A18Rik, Records as Topics, epsilon-diaminocaproic acid, proteins, ions, man, ASN, Travel Documents, Asn, CD156, Probabilities, OCTD, Asparagin, LYS, 2-amino-4-(methylthio)butanoic acid, 10^[-6], Lysin, ppm, peptidos, L-Glutamine, Half Cystine, metionina, GPHYSD2, Racemethionine, drug tolerance, thiol methyltransferase activity, SGS, ratio, data, Zinc Cysteinate, DL-Methionine, protein complex, immune system tolerance, T5E21.12, Proteins, 2-Amino-4-(methylthio)butyric acid, total expressed protein, Personal Identification Systems, L-2-Aminoglutaramic acid, L-Isomer, Peptide, ACMICD, polypeptide, S-adenosyl-L-methionine:thiol S-methyltransferase activity, native protein, Immune Tolerance, natural protein, Ionen, Acetate, Protein, lysine, Glutamic acid 5-amide, Immunologic Tolerance, sequence, mixed synapse, Methionin, MFS1, methionine, Hmet, L-Glutamin, L-Lysine, fixed, tandem MS, Data Base, Met, WMS2, teratoma with malignant transformation, L Glutamine, T5E21_12, parent ion, Col4a-1, Glutamic acid amide, MS/MS, proportionality, Tripcellim, rate, Records as Topic, L-Cysteine, alpha, MASS, 2-amino-3-carbamoylpropanoic acid, (S)-2, Record, CD156a, beta Trypsin, 4-diamino-4-oxobutanoic acid, human, primary structure of sequence macromolecule, L-glutamic acid gamma-amide, Protein Gene Products, Trypure, Gene Proteins, synaptic junction, Self Tolerance, D Glutamine, precursor ion, Tolerance, Identification Systems, Ion, SSKS, Personal Identification System, alpha-amino-gamma-methylmercaptobutyric acid, quotient, electrotonic synapse, Travel, Peptid, Polypeptide, 6-diaminohexanoic acid, TMT, Liquimeth, Proteomes, Enisyl, Peptide., Immunological ToleranceParkinson's disease, deceased, type 2, Materials, Activity, methionine aminopeptidase activity, Laboratory, Parkinson's disease NOS, protein, Cardiac Death, Lobus Frontalis, protein polypeptide chains, diseases, Paralysis Agitans, 2, diseases and disorders, synganglion, Analysis, Research Activity, Frontal, protein aggregate, Laboratory Research, WMS, peptidase M activity, Mass Spectrum Analysis, adenomas, Priorities, rabGAPLP, human disease, L-methionine aminopeptidase activity, Frontal Cortex, Parkinson disease, dermoid cyst with malignant transformation, Parkinson's disease (disorder), Analyses, Tissue, RabGAP-5, Neuropathologists, proteins, suprasegmental levels of nervous system, lobus frontalis, Frontal Cortices, Brodmann Area 8, RUSC3, scientific observation, signaling process, Homo sapiens disease, Parkinson syndrome, Research Priority, GPHYSD2, Reference Standard, SGS, single organism signaling, Parkinson's syndrome, Brodmann's, Parkinsons, Standard Preparation, Standard Preparations, suprasegmental structures, Standardization, Data Set, MYH-associated polyposis, autosomal recessive familial adenomatous polyposis, Maps, Research Priorities, Neuropathologist, Spectrum Analysis, Frontal Eye Fields, regio frontalis, ACMICD, Spectroscopy, any method, S-adenosyl-L-methionine:thiol S-methyltransferase activity, Idiopathic Parkinson's Disease, batch, frontal lobe cortex, Lewy Body Parkinson Disease, Diseases, Genetic Materials, overlap, Genetic Material, autosomal recessive, Research and Development, MUTYH-associated polyposis, MUTYH-related AFAP, RUTBC3, frontal region, Standard, Encephalon, Brodmanns Area 8, Spectrometry, frontal neocortex, common, INSDC_feature:gene, MASS, Supplementary, human, RABGAP5, Activities, disease, Area 8, Patient, Supplementary Eye Fields, paralysis agitans, Material, Neuropathologies, multiple colorectal, MUTYH-related attenuated familial polyposis coli, Cistron, TMT, cortex of frontal lobe, gray matter of frontal lobe, the brain, Lobe, other disease, biological signaling, human being, Lewy Body, number, FBN, Gene, Spectrum Analyses, protein-containing complex, presence, polypeptide chain, ECTOL1, lobi frontales, Brodmann's Area 8, Mass, disease or disorder, familial adenomatous polyposis, Mass Spectroscopy, MAP, Genetic, Research, MS3, familial adenomatous polyposis 2, frontal cortex, Frontal Eye Field, Eye Field, man, study assay, Idiopathic PD, non-neoplastic, OCTD, autosomal recessive multiple colorectal adenomas, Reference, Idiopathic, Clients, Parkinson Disease, Parkinsonism, disorder, Development and Research, Preparation, Supplementary Eye Field, thiol methyltransferase activity, measuring, MUTYH-related attenuated familial adenomatous polyposis, Primary Parkinsonism, MUTYH-Associated Polyposis, protein complex, disorders, medical condition, Primary, Cistrons, Client, encephalon, Idiopathic Parkinson Disease, count in organism, Priority, Cortex, native protein, natural protein, Parkinson's Disease, Brodmann, MUTYH-related attenuated FAP, Protein, proteomic analysis, post-mortem, Research Activities, condition, MFS1, Death, grey matter of frontal lobe, Mass Spectrum Analyses, WMS2, teratoma with malignant transformation, Mass Spectrum, centric, distinct., PARK, MYH-Associated Polyposis, signalling, Lewy Body Parkinson's Disease, Parkinsonian disorder, Eye Fields, Preparations, signalling process, Parkinson's disease NOS (disorder), SSKS, Standards, MAP syndrome, quantitative, Frontal Lobes, FAP2, presence or absence in organism, colorectal adenomatous polyposisPresenile Alzheimer Dementia, Parkinson's disease, deceased, type 2, ALZHEIMERS DIS, stiff-person syndrome, Materials, Activity, methionine aminopeptidase activity, Laboratory, Early Onset, Parkinson's disease NOS, selection process, protein, Cardiac Death, progressive encephalomyelitis with rigidity, Alzheimer's disease, Lobus Frontalis, ischiocoxopodopatellar syndrome, Morsch Woltman syndrome, stiff man syndrome, AD, protein polypeptide chains, unspecified, AW111620, diseases, small patella syndrome, congenital coxa vara, sucrose phosphate synthetase activity, 2, diseases and disorders, synganglion, Analysis, Research Activity, Frontal, protein aggregate, Laboratory Research, WMS, tarsal synostosis, peptidase M activity, AI505014, Mass Spectrum Analysis, adenomas, Priorities, rabGAPLP, LATE ONSET ALZHEIMER DIS, human disease, L-methionine aminopeptidase activity, Frontal Cortex, Parkinson disease, dermoid cyst with malignant transformation, DAT - Dementia Alzheimer's type, Parkinson's disease (disorder), Analyses, UDP-glucose-fructose-phosphate glucosyltransferase activity, Tissue, RabGAP-5, Neuropathologists, coxopodopatellar syndrome, proteins, suprasegmental levels of nervous system, lobus frontalis, Frontal Cortices, Brodmann Area 8, AD - Alzheimer's disease, RUSC3, scientific observation, Alzheimer Type Dementia, Homo sapiens disease, ALZHEIMER DIS EARLY ONSET, Parkinson syndrome, Research Priority, Presenile, GPHYSD2, Reference Standard, Alzheimers disease, Scott-Taor syndrome, SGS, AA589574, sucrose phosphate-uridine diphosphate glucosyltransferase activity, 1110046B24Rik, Parkinson's syndrome, Brodmann's, Senile, Parkinsons, Standard Preparation, Standard Preparations, suprasegmental structures, Standardization, Data Set, Acute Confusional Senile Dementia, ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, MYH-associated polyposis, autosomal recessive familial adenomatous polyposis, Maps, Research Priorities, Neuropathologist, Spectrum Analysis, Frontal Eye Fields, Alzheimer's Dementia, regio frontalis, Stiff man syndrome, ACMICD, Alzheimer Type, Spectroscopy, any method, S-adenosyl-L-methionine:thiol S-methyltransferase activity, batch, frontal lobe cortex, Diseases, Genetic Materials, NOS, overlap, uridine diphosphoglucose-fructose phosphate glucosyltransferase activity, Genetic Material, autosomal recessive, Dementia, parent ion, Research and Development, MUTYH-associated polyposis, MUTYH-related AFAP, RUTBC3, Alzheimers, frontal region, Standard, Alzheimer, Encephalon, Brodmanns Area 8, Spectrometry, frontal neocortex, common, Dementias, INSDC_feature:gene, MASS, Supplementary, ICPPS, human, RABGAP5, MRSR, Activities, disease, Area 8, Senile Dementia, precursor ion, Patient, Supplementary Eye Fields, paralysis agitans, Material, Neuropathologies, multiple colorectal, MUTYH-related attenuated familial polyposis coli, Cistron, Alzheimer's Disease, TMT, cortex of frontal lobe, Dementia of the Alzheimer's type, gray matter of frontal lobe, the brain, Lobe, other disease, common., sucrose 6-phosphate synthase activity, human being, ischiopatellar dysplasia, Stiff-trunk syndrome, number, FBN, Gene, precursor, Spectrum Analyses, Focal Onset, protein-containing complex, presence, unspecified (disorder), ALZHEIMER DIS, UDPglucose-fructose-phosphate glucosyltransferase activity, [X]Dementia in Alzheimer's disease, polypeptide chain, UDP-glucose:D-fructose-6-phosphate 2-alpha-D-glucosyltransferase activity, ECTOL1, lobi frontales, Brodmann's Area 8, Mass, disease or disorder, Coxo-podo-patellar syndrome, SMS, Moersch-Woltman syndrome, familial adenomatous polyposis, Mass Spectroscopy, MAP, SPMSY, patella aplasia, Genetic, sucrosephosphate-UDP glucosyltransferase activity, Research, MS3, familial adenomatous polyposis 2, frontal cortex, Frontal Eye Field, labeling, Eye Field, man, study assay, Idiopathic PD, FOCAL ONSET ALZHEIMERS DIS, non-neoplastic, OCTD, autosomal recessive multiple colorectal adenomas, Stiff-man syndrome (disorder), UDPglucose:D-fructose-6-phosphate 2-alpha-D-glucosyltransferase activity, Reference, Stiff-Person Syndrome, Clients, Alzheimer Disease, SELD, disorder, Alzheimer's disease (disorder), Development and Research, Preparation, SpS, Alzheimers Dementia, Supplementary Eye Field, thiol methyltransferase activity, SPS1, coxa vara, Alzheimer Senile Dementia, Stiff person syndrome and related disorders, measuring, MUTYH-related attenuated familial adenomatous polyposis, Disease, STIFF-PERSON syndrome, MUTYH-Associated Polyposis, protein complex, disorders, medical condition, SPS, Cistrons, Client, encephalon, Primary Senile Degenerative Dementia, Stiff Person syndrome, [X]Dementia in Alzheimer's disease (disorder), Stiff-man syndrome, count in organism, Priority, Cortex, native protein, natural protein, Brodmann, MUTYH-related attenuated FAP, Protein, proteomic analysis, post-mortem, Research Activities, condition, MFS1, Death, grey matter of frontal lobe, Mass Spectrum Analyses, WMS2, teratoma with malignant transformation, Stiff-Man syndrome, Mass Spectrum, Dementia in Alzheimer's disease, Alzheimer's Disease Pathway, SRS, MYH-Associated Polyposis, Alzheimer Dementia, Parkinsonian disorder, Eye Fields, Preparations, Late Onset, Parkinson's disease NOS (disorder), Dementia in Alzheimer's disease (disorder), SSKS, Standards, MAP syndrome, patella aplasia and tarsal synostosis, quantitative, Frontal Lobes, FAP2, presence or absence in organism, colorectal adenomatous polyposisthe brain, other disease, human disease, suprasegmental structures, human being, determination, Encephalon, number, disorders, total expressed protein, suprasegmental levels of nervous system, man, presence, encephalon, human, non-neoplastic, disease, count in organism, diseases, chemical analysis, Diseases, disease or disorder, condition, disorder, Homo sapiens disease, diseases and disorders, medical condition., synganglion, assay, quantitative, Proteomes, presence or absence in organism380trueGlobal quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s DiseasePatients with Alzheimer’s disease (AD) and Parkinson disease (PD) often have overlap in brain neuropathology and clinical presentation suggesting that these two diseases share common underlying mechanisms. Currently, the molecular events linking AD and PD are incompletely understood. Utilizing 10-plex Tandem Mass Tag (TMT) assays and MultiNotch MS3 mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as healthy controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11,840 protein groups representing 10,230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra-batch and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of protein signatures and neuro-centric signaling pathways that are common or distinct in AD and PD.2018-02-072017-07-31PXD0071602806551646099180498511145422492156843544071284218327042363336351198343006636362758385696363121766668888111430155571145263145262364934613126957366649239161936413645106656889511363647627236611123294422295558326813042323122586365434607925193659106321432059712938655819125023254537111957748186619682158672256807617554373592536685862740816918045427877512010892250583674147956410039236942049433445974142001258641935293NCBITaxon:77643671567593643867716054048313152826930456271639162429204277944762376369612181003296292211376394863948840479NCBITaxon:215713152731051067125027820596875497792016516368407173630969893610478214836432042929410106132049138169374327732046640707453511110310780621745921612928867128867641006945694101676341021076127735113165821358430141729817463367541287356756840301350621813019411192943936711041136445913949843202530127032022149875110475941204788613474951537211097165299827905135551398031758543980126086639808137575551832019644719821114155421932555211383439119318198139818102697026635311069955529NCBITaxon:47518502983354764146547798251021691572739823897648407413735186287054824153NCBITaxon:505579844675251000364334147548021035974137081154665478983532215998381067710348198523487804225314884142228632266347946157187125939915991915729529292117527198601488406334249518691234235238152335985898598865597464998703920211107263990363527215987419082874394232418235024145113969293190259390719017463601237474636172262536001319722119158531058859698951105198997237989772000263419610264266722758858156899628737562690724420237172019998570724074767927459615333554319311671833554184005136861505968666211961748666134751536329NCBITaxon:17632862871103411033348837670580271848186536859598607575527472036105135294296110098402321000734882412336363071047005187878945556449447NCBITaxon:13356262664955419591399878168119011478281055524NCBITaxon:96063181781358584690081366848197915351930728593008526411409005118499526225412133759139014381113944235084370416744312044143708351581990119519532590841370137023943222774862615835583715371633376057267998086371137121906503714759172073127262981274575727090309031637910372814243371421044792491108239412NCBITaxon:9615658858147802692661006581373527504541356638164752037506442236695021293497905463224555253651997649908143899237453747264732376026473128870559553614169152527403271602938511497864794363755293824794372251177529912044741673872175091938441376593934347393271591002263767423444234546700128768959119846704146479293652803428038280351080348330779179392112621229502711311803738681911265269971028622527391076015973611432425071140981087135547743658142450722953379698204232124223321803369822347081645733185889716546759928777020382931412529550811481744888643745264999728303571830855071762997076789268370415156288765138856392456115293202086595551655181135491432137159749535026143213858781707683194963401614280053164686275110466038151845474485009747697477118051240174841855601555479204274381513201488711053253297261005941289093164351211604990013894382835423242331082934122058560416299131122731701879915429131267818187104931640729946714423683033373304852646383011306413992530642369923121162065261610337286129940207340115357652611114716133865431201725323712552329935316317NCBITaxon:11084993841063267872862321933486208621160791392227681196125522814953932132232334774121827532917573129948861814084341033519963139248913924881153381153393304393755699286265599339112094886241571839975864442374864353324442606653324134390976821271786371979856863999839986865535291486541042986357358257632884019864982380111911028688999586652203411508599632138119380625631886571303443112130886581144889198466645463NCBITaxon:11072NCBITaxon:11071142800628835374375116597145943116598854331116781077854314408043933434NCBITaxon:11082693977381382189931824431935128387145953116885311213278695berry8694100333586972443664701501114286921504751499105484204714722354025120847014649744497431170089306218644193061107632330805660396016217974825853946055396513212790568813377512981766378876017112147861050236694657349632051124501897441739412450128853183889198679488531911137910371647351660152943631631198573896939343237956026087121346334323223544314275241433611334565560291699636436802790105603140818838185733703401881274414936530437552196969716203871398558408172405598609183827275921274423408170275981274420127442623545513656531762793821176275943282474801199150956481882291690255120455148167238473848190695148498101510693731263753405203860186497405224052141856451804NCBITaxon:813478009152275484793870333849387191722617561094616143512032581205505235259447320549386411257226512165125388037668612067811220223074322011867051186705738733486912193879186802398007186801215451468351408186150847120677769183885160861138886915216778672127901008704351231719692812392948677133154845422612621981318826824112292657163295769381247124614854513283883483929491139036312041626658907715148800369426941694369451879010150808170539420654210556873174471270153292428141119466911696014545869532010198126469055053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