{"database":"GPMDB","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":24,"searchCount":5},"additional":{"omics_type":["Other"],"submitter":["Dislich B, et al."],"instrument_platform":["Instrument"],"disease":["Not Available"],"brenda_tissue":["Not available"],"species":["Mus_musculus_viruses, Mouse"],"submitter_mail":["stefan.lichtenthaler@dzne.de"],"publication":["26139848"],"submitter_affiliation":["German Center for Neurodegenerative Diseases (DZNE), Munich, et al."],"model":["http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025079","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025078","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025075","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025076","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025073","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025074","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025082","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025083","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025080","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025081","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025069","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025088","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025089","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025086","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025087","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025084","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025085","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025093","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025071","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025072","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025094","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025091","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025070","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025092","http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310025090"],"cell_type":["Not available"],"repository":["GPMDB"],"pubmed_abstract":["Analysis of murine cerebrospinal fluid (CSF) by quantitative mass spectrometry is challenging because of low CSF volume, low total protein concentration, and the presence of highly abundant proteins such as albumin. We demonstrate that the CSF proteome of individual mice can be analyzed in a quantitative manner to a depth of several hundred proteins in a robust and simple workflow consisting of single ultra HPLC runs on a benchtop mass spectrometer. The workflow is validated by a comparative analysis of BACE1-/- and wild-type mice using label-free quantification. The protease BACE1 cleaves the amyloid precursor protein (APP) as well as several other substrates and is a major drug target in Alzheimer's disease. We identified a total of 715 proteins with at least 2 unique peptides and quantified 522 of those proteins in CSF from BACE1-/- and wild-type mice. Several proteins, including the known BACE1 substrates APP, APLP1, CHL1 and contactin-2 showed lower abundance in the CSF of BACE1-/- mice, demonstrating that BACE1 substrate identification is possible from CSF. Additionally, ectonucleotide pyrophosphatase 5 was identified as a novel BACE1 substrate and validated in cells using immunoblots and by an in vitro BACE1 protease assay. Likewise, receptor-type tyrosine-protein phosphatase N2 and plexin domain-containing 2 were confirmed as BACE1 substrates by in vitro assays. Taken together, our study shows the deepest characterization of the mouse CSF proteome to date and the first quantitative analysis of the CSF proteome of individual mice. The BACE1 substrates identified in CSF may serve as biomarkers to monitor BACE1 activity in Alzheimer patients treated with BACE inhibitors."],"pubmed_title":["Label-free Quantitative Proteomics of Mouse Cerebrospinal Fluid Detects β-Site APP Cleaving Enzyme (BACE1) Protease Substrates In Vivo."],"pubmed_authors":["Dislich Bastian B,Wohlrab Felix F,Bachhuber Teresa T,Müller Stephan A SA,Kuhn Peer-Hendrik PH,Hogl Sebastian S,Meyer-Luehmann Melanie M,Lichtenthaler Stefan F SF,","Dislich Bastian B, Wohlrab Felix F, Bachhuber Teresa T, Müller Stephan A SA, Kuhn Peer-Hendrik PH, Hogl Sebastian S, Meyer-Luehmann Melanie M, Lichtenthaler Stefan F SF"],"name_synonyms":["Amyloid intracellular domain 57, aspartyl protease 2, APP, 3.4.22.-, Amyloid intracellular domain 59, ABETA, Laboratory, P3(40), Mus domesticus, number, A4, CTFgamma, mini-ICE, CASP-14, betaApp, Amyloid intracellular domain 50, presence, House Mouse, Abpp, HSPC104, Cerebrospinal, AID(59), AAA, Cvap, AG, cerebral spinal fluid, Beta-amyloid protein 42, cerebral vascular amyloid peptide, House, APP-C57, APP-C59, Beta-amyloid protein 40, alzheimer disease amyloid protein, Mus musculus domesticus, Cerebro Spinal, protease nexin-II, liquor cerebrospinalis, amyloidogenic glycoprotein, Mice, AID(50), memapsin-2, Ag, PreA4, Swiss, S-APP-beta, Swiss Mice, Gamma-CTF(59), \"mouse\" EXACT common_name [], free, beta-site APP cleaving enzyme 1, Alzheimer disease amyloid A4 protein homolog, \"Mus muscaris\" RELATED misnomer [], N-APP, AID(57), Gamma-secretase C-terminal fragment 50, Gamma-secretase C-terminal fragment 57, Gamma-secretase C-terminal fragment 59, AD1, \"mice C57BL/6xCBA/CaJ hybrid\" RELATED misspelling [], Abeta, house mouse, APPI, C80, C83, Cerebro Spinal Fluid, Amyloidogenic glycoprotein, AICD-50, ASP2, S-APP-alpha, E030013M08Rik, mouse, Fluids, Cerebrospinal Fluids, spinal fluid, Gamma-CTF(57), mice C57BL/6xCBA/CaJ hybrid, Spinal Fluid, Mus muscaris, Cerebro Spinal Fluids, Gamma-CTF(50), C99, APP-C99, Spinal Fluids, count in organism, Fluid, count, Mus, Adap, BACE., Mini-ICE, AICD-57, BACE1, AICD-59, Cerebral vascular amyloid peptide, Mus musculus, P3(42), PN-II, Caspase-14 subunit p10, mice, membrane-associated aspartic protease 2, Swiss Mouse, beta-site amyloid precursor protein cleaving enzyme 1, House Mice, Caspase-14 subunit p19, Soluble APP-beta, CSF, alzheimer disease amyloid A4 protein homolog, Alzheimer disease amyloid protein, MICE, Cerebro, Protease nexin-II, Laboratory Mice, domesticus, C31, \"house mouse\" EXACT genbank_common_name [], Soluble APP-alpha, Mouse, Beta-APP42, PN2, quantitative, Beta-APP40, Laboratory Mouse, CVAP, presence or absence in organism, ABPP"],"description_synonyms":["OCT, 3.4.22.-, CSF2, data, PlexA2, mol, PLXN2, Laboratory, Mus domesticus, Proteins, mouse, number, HPLC., Gene, GM-CSF, mini-ICE, CASP-14, spinal fluid, AA589422, House Mouse, presence, Cell, polypeptide, count in organism, Workflows, AW457381, cerebral spinal fluid, count, House, Mus, Sargramostim, PIG7, Mini-ICE, Protein, GRIM-12, colony-stimulating factor, Gene Products, Mus musculus domesticus, liquor cerebrospinalis, Work Flow, Mice, GMCSF, Mus musculus, Caspase-14 subunit p10, cell, Swiss, mice, Swiss Mouse, molgramostin, 2810428A13Rik, House Mice, Swiss Mice, Caspase-14 subunit p19, proteins, CSF, Colony-stimulating factor, Csfgm, MICE, sargramostim, Laboratory Mice, domesticus, Protein Gene Products, Gene Proteins, Molgramostin, TrxR1, TXNR, TR1, Mouse, quantitative, SIMPLE, Plxn2, mKIAA0463, Proteomes, Laboratory Mouse, Work Flows, TR, TRXR1, presence or absence in organism, TP53I7"],"pubmed_title_synonyms":["Amyloid intracellular domain 57, aspartyl protease 2, APP, 3.4.22.-, Amyloid intracellular domain 59, ABETA, Laboratory, P3(40), Mus domesticus, number, A4, CTFgamma, mini-ICE, CASP-14, betaApp, Amyloid intracellular domain 50, presence, House Mouse, Abpp, HSPC104, Cerebrospinal, AID(59), AAA, Cvap, AG, cerebral spinal fluid, Beta-amyloid protein 42, cerebral vascular amyloid peptide, House, APP-C57, APP-C59, Beta-amyloid protein 40, alzheimer disease amyloid protein, Mus musculus domesticus, Cerebro Spinal, protease nexin-II, liquor cerebrospinalis, amyloidogenic glycoprotein, Mice, AID(50), memapsin-2, Ag, PreA4, Swiss, S-APP-beta, Swiss Mice, Gamma-CTF(59), \"mouse\" EXACT common_name [], free, beta-site APP cleaving enzyme 1, Alzheimer disease amyloid A4 protein homolog, \"Mus muscaris\" RELATED misnomer [], N-APP, AID(57), Gamma-secretase C-terminal fragment 50, Gamma-secretase C-terminal fragment 57, Gamma-secretase C-terminal fragment 59, AD1, \"mice C57BL/6xCBA/CaJ hybrid\" RELATED misspelling [], Abeta, house mouse, APPI, C80, C83, Cerebro Spinal Fluid, Amyloidogenic glycoprotein, AICD-50, ASP2, S-APP-alpha, E030013M08Rik, mouse, Fluids, Cerebrospinal Fluids, spinal fluid, Gamma-CTF(57), mice C57BL/6xCBA/CaJ hybrid, Spinal Fluid, Mus muscaris, Cerebro Spinal Fluids, Gamma-CTF(50), C99, APP-C99, Spinal Fluids, count in organism, Fluid, count, Mus, Adap, BACE., Mini-ICE, AICD-57, BACE1, AICD-59, Cerebral vascular amyloid peptide, Mus musculus, P3(42), PN-II, Caspase-14 subunit p10, mice, membrane-associated aspartic protease 2, Swiss Mouse, beta-site amyloid precursor protein cleaving enzyme 1, House Mice, Caspase-14 subunit p19, Soluble APP-beta, CSF, alzheimer disease amyloid A4 protein homolog, Alzheimer disease amyloid protein, MICE, Cerebro, Protease nexin-II, Laboratory Mice, domesticus, C31, \"house mouse\" EXACT genbank_common_name [], Soluble APP-alpha, Mouse, Beta-APP42, PN2, quantitative, Beta-APP40, Laboratory Mouse, CVAP, presence or absence in organism, ABPP"],"pubmed_abstract_synonyms":["aspartyl protease 2, Amyloid intracellular domain 57, APP, Amyloid intracellular domain 59, ABETA, Presenile Alzheimer Dementia, Astrin, para Tyrosine, Viral Marker, Biological Markers, ALZHEIMERS DIS, Surrogate Endpoints, determination, Laboratory, Nrln1, Early Onset, Mus domesticus, Biochemical, A4, 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disease, scientific observation, Gamma-secretase C-terminal fragment 59, Tyr, Viral Markers, Alzheimer Type Dementia, AD1, Abeta, \"mice C57BL/6xCBA/CaJ hybrid\" RELATED misspelling [], ALZHEIMER DIS EARLY ONSET, APPI, house mouse, Presenile, SIMPLE, C80, Alzheimers disease, C83, Cerebro Spinal Fluid, Senile, CHL, sporadic Alzheimer's disease, Viral, AICD-50, Surrogate Endpoint, S-APP-alpha, Acute Confusional Senile Dementia, mouse, 2-Amino-3-(p-hydroxyphenyl)propionic acid, CHL1, Biochemical Markers, para-Tyrosine, Tl3, Gamma-CTF(57), Tl2, Biologic Marker, Spectrum Analysis, Alzheimer's Dementia, mice C57BL/6xCBA/CaJ hybrid, Tyrosine, Cerebro Spinal Fluids, Spectroscopy, Alzheimer Type, Amyloid Fibrils, C99, any method, Workflows, AI874642, count, Marker, PIG7, BACE., Mini-ICE, BACE1, AICD-57, Mastrin, NOS, WABS, LICAM2, Protein phosphatase, AICD-59, Dementia, Cerebral vascular amyloid peptide, Mus musculus, Amyloid Substance, Alzheimers, Caspase-14 subunit p10, End Points, mice, membrane-associated aspartic protease 2, Alzheimer, Swiss Mouse, L-isomer, Spectrometry, Identifications (Psychology), Dementias, Caspase-14 subunit p19, alzheimer disease amyloid A4 protein homolog, Immunologic, Alzheimer disease amyloid protein, Colony-stimulating factor, Csfgm, Laboratory Marker, Cerebro, MICE, Protease nexin-II, domesticus, Alzheimer's, L isomer, DMDA, Senile Dementia, Patient, Biochemical Marker, Mouse, L-Tyrosine, Alzheimer's Disease, Proteomes, Work Flows, BACE, Dementia of the Alzheimer's type, Xenopus, 3.4.22.-, CSF2, Clinical Markers, P3(40), Clinical Marker, number, Gene, Mitotic spindle-associated protein p126, GM-CSF, mini-ICE, Spectrum Analyses, betaApp, Focal Onset, presence, TYPE, unspecified (disorder), Cerebrospinal, Surrogate End Points, DAGA4, AID(59), ALZHEIMER DIS, Surrogate Markers, [X]Dementia in Alzheimer's disease, House, APP-C57, APP-C59, colony-stimulating factor, Mass, Gene Products, alzheimer disease amyloid protein, Cerebro Spinal, Mus 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File: CSF124WT_50cm_TR1.mzml. Published as part of Mol Cell Proteomics. 2015 Oct;14(10):2550-63  . From the Abstract: {{i}} ... We demonstrate that the CSF proteome of individual mice can be analyzed in a quantitative manner to a depth of several hundred proteins in a robust and simple workflow consisting of single ultra HPLC runs on a benchtop mass spectrometer ... {{/i}}","dates":{"submission":"2015-10-12"},"accession":"GPM32310025075","cross_references":{"pubmed":["26139848"],"Pride":["PXD001514"],"pride":[],"Pride Archive":["PXD001514"]}}