ArticleClinical proteomics2019
Deep undepleted human serum proteome profiling toward biomarker discovery for Alzheimer's disease.
Article in Clinical proteomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 134 citations in OpenAlex.
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- Integrated Structural and Glycoproteomic Profiling Reveals Protein Conformational Remodeling and Biomarkers Across Alzheimer's Disease Progression.ACS central science · 2026Article
- Streamlined resource-efficient plasma amyloid-beta mass spectrometry assay has improved biomarker performance in preclinical Alzheimer's disease.Nature communications · 2026Article
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- SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.Current opinion in lipidology · 2025Review
- Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Proteomic landscape of Alzheimer's disease: emerging technologies, advances and insights (2021 - 2025).Molecular neurodegeneration · 2025Review
- Multi-omic serum analysis reveals ferroptosis pathways and diagnostic molecular signatures associated with Moyamoya diseases.Journal of neuroinflammation · 2025Article
- Comprehensive analysis of blood proteome response to necrotic enteritis in broiler chicken.Veterinary research · 2025Article
- Selected Ion Extraction of Peptides with Heavy Isotopes and Hydrogen Loss Reduces the Type II Error in Plasma Proteomics.ACS omega · 2025Article
- The aggregate proteome ofFrontiers in aging neuroscience · 2025Article
- Molecular insights into the unique properties of the blood-circulating proteasome.Journal of extracellular biology · 2025Article
- Cognitive decline in older adults with type 2 diabetes: Unraveling site-specific glycoproteomic alterations.PloS one · 2025Article
- The early diagnosis of Alzheimer's disease: Blood-based panel biomarker discovery by proteomics and metabolomics.CNS neuroscience & therapeutics · 2024Review
- Site-specific immobilization of the endosialidase reveals QSOX2 is a novel polysialylated protein.Glycobiology · 2024Article
- Pla2g12b drives expansion of triglyceride-rich lipoproteins.Nature communications · 2024Article
- Alzheimer's-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets.iScience · 2024Article
- Plasma/Serum Proteomics based on Mass Spectrometry.Protein and peptide letters · 2024Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBlood-based protein measurement is a routine practice for detecting biomarkers in human disease. Comprehensive profiling of blood/plasma/serum proteome is a challenge due to an extremely large dynamic range, as exemplified by a small subset of highly abundant proteins. Antibody-based depletion of these abundant proteins alleviates the problem but introduces experimental variations. We aimed to establish a method for direct profiling of undepleted human serum and apply the method toward biomarker discovery for Alzheimer's disease (AD), as AD is the most common form of dementia without available blood-based biomarkers in clinic.
methodsWe present an ultra-deep analysis of undepleted human serum proteome by combining the latest 11-plex tandem-mass-tag (TMT) labeling, exhaustive two-dimensional liquid chromatography (LC/LC) fractionation (the 1st LC: 3 h for 180 fractions, and the 2nd LC: 3 h gradient per fraction), coupled with high resolution tandem mass spectrometry (MS/MS). AD (
resultsThe TMT-LC/LC-MS/MS platform is capable of analyzing 4826 protein components (4368 genes), covering at least 6 orders of magnitude in dynamic range, representing one of the deepest serum proteome analysis. We defined intra- and inter- group variability in the AD and control groups. Statistical analysis revealed differentially expressed proteins in AD (26 decreased and 4 increased). Notably, these altered proteins are enriched in the known pathways of mitochondria, fatty acid beta oxidation, and AGE/RAGE. Finally, we set up a TOMAHAQ method to confirm the decrease of PCK2 and AK2 in our AD samples.
conclusionsOur results show an ultra-deep serum discovery study by TMT-LC/LC-MS/MS, and a validation experiment by TOMAHAQ targeted LC-MS3. The MS-based discovery and validation methods are of general use for biomarker discovery from complex biofluids (e.g. serum proteome). This pilot study also identified deregulated proteins, in particular proteins associated with mitochondrial function in the AD serum samples. These proteins may serve as novel AD candidate biomarkers.
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