ArticleMolecular & cellular proteomics : MCP2015
Label-free Quantitative Proteomics of Mouse Cerebrospinal Fluid Detects β-Site APP Cleaving Enzyme (BACE1) Protease Substrates In Vivo.
Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- Design and development of lipid nanoparticle formulations for brain gene therapy.Molecular therapy. Nucleic acids · 2026Article
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- Elenbecestat and Compound 89 Potently Inhibit BACE1 but Not BACE2 When Subchronically Dosed in Non-Human Primates.Proteomics · 2026Article
- A novel vector design targeting the blood-brain barrier with the brain-specific AAV-BR1 vector enables abluminal protein secretion from brain endothelial cells in vitro.Fluids and barriers of the CNS · 2025Article
- The lysosomal catabolism of nucleic acids-critical regulators of the innate immune system.Nucleic acids research · 2025Review
- CSF protein ratios with enhanced potential to reflect Alzheimer's disease pathology and neurodegeneration.Molecular neurodegeneration · 2024Article
- A methodology to globally assess ectodomain shedding using soluble fractions from the mouse brain.Frontiers in psychiatry · 2024Article
- BACE1 regulates expression of Clusterin in astrocytes for enhancing clearance of β-amyloid peptides.Molecular neurodegeneration · 2023Article
- The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.Molecular neurodegeneration · 2023Article
- Targeted BACE-1 inhibition in microglia enhances amyloid clearance and improved cognitive performance.Science advances · 2022Article
- BACE-1 inhibition facilitates the transition from homeostatic microglia to DAM-1.Science advances · 2022Article
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- Intercellular signaling by ectodomain shedding at the synapse.Trends in neurosciences · 2022Review
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Nature aging · 2022Article
- PTPRD and DCC Are Novel BACE1 Substrates Differentially Expressed in Alzheimer's Disease: A Data Mining and Bioinformatics Study.International journal of molecular sciences · 2022Article
- Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer's disease.Molecular neurodegeneration · 2022Article
- The β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.Molecular neurobiology · 2022Article
- Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory.Frontiers in molecular neuroscience · 2022Article
- Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model.Molecules (Basel, Switzerland) · 2021Article
- Novel Alzheimer's disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers.Translational psychiatry · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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