PXD001514

PXD001514 is an original dataset announced via ProteomeXchange.

Title	BACE1 KO mouse CSF LC-MSMS
Description	Analysis of murine cerebrospinal fluid (CSF) by quantitative mass spectrometry is challenging due to 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 by immunoblot and in vitro BACE1 protease assay. 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.
HostingRepository	PRIDE
AnnounceDate	2015-10-12
AnnouncementXML	Submission_2015-10-12_00:44:51.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan Mueller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2014-11-19 05:58:30	ID requested
⏵ 1	2015-10-12 00:44:52	announced

Dislich B, Wohlrab F, Bachhuber T, M, ü, ller SA, Kuhn PH, Hogl S, Meyer-Luehmann M, Lichtenthaler SF, -Site APP Cleaving Enzyme (BACE1) Protease Substrates In Vivo. Mol Cell Proteomics, 14(10):2550-63(2015) [pubmed]

curator keyword: Biological

submitter keyword: Mouse CSF, CSF, label-free quantification

Stefan Lichtenthaler
contact affiliation	German Center for Neurodegenerative Diseases (DZNE) Munich Department of Neuroproteomics Feodor-Lynen-Str. 17 81377 Munich Germany
contact email	stefan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliation	DZNE Munich Neuroproteomics
contact email	stephan.mueller@dzne.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001514
     1. Label: PRIDE project
     2. Name: BACE1 KO mouse CSF LC-MSMS