SynthesisMolecular & cellular proteomics : MCP2023
Dissecting Detergent-Insoluble Proteome in Alzheimer's Disease by TMTc-Corrected Quantitative Mass Spectrometry.
Synthesis in Molecular & cellular proteomics : MCP, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Orthogonal Ionic Liquid-Based Extraction Strategy Enables Amyloid-Specific Profiling of Aggregate Proteome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Single Plaque Proteomics Reveals the Composition and Dynamics of the Amyloid Microenvironment in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Neuronal subtype governs amyloid structure, cellular response, and cognitive outcome in genetically targeted APP mouse models.Molecular neurodegeneration · 2026Article
- Proteostasis network response to environmental chronic stress: linking survival to protein aggregation in a human neuroblastoma cellular model.Cellular and molecular life sciences : CMLS · 2025Article
- Pharmacologic inhibition of PCBP2 biomolecular condensates relieves Alzheimer's disease.Nature communications · 2025Article
- Midkine attenuates amyloid-β fibril assembly and plaque formation.Nature structural & molecular biology · 2025Article
- Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer's Disease.Biomolecules · 2025Review
- Proteomic landscape of Alzheimer's disease: emerging technologies, advances and insights (2021 - 2025).Molecular neurodegeneration · 2025Review
- Human and mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome.Nature communications · 2025Article
- Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia.Brain, behavior, & immunity - health · 2024Article
- Human-mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome.bioRxiv : the preprint server for biology · 2024Article
- Transgenic sensors reveal compartment-specific effects of aggregation-prone proteins on subcellular proteostasis during aging.Cell reports methods · 2024Article
- A Tutorial Review of Labeling Methods in Mass Spectrometry-Based Quantitative Proteomics.ACS measurement science au · 2024Review
- Evaluation of Protein Identification and Quantification by the diaPASEF Method on timsTOF SCP.Journal of the American Society for Mass Spectrometry · 2024Article
- Clinical Proteomics: A Promise Becoming Reality.Molecular & cellular proteomics : MCP · 2024Article
- A Causal Model of Ion Interference Enables Assessment and Correction of Ratio Compression in Multiplex Proteomics.Molecular & cellular proteomics : MCP · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Protein aggregation of amyloid-β peptides and tau are pathological hallmarks of Alzheimer's disease (AD), which are often resistant to detergent extraction and thus enriched in the insoluble proteome. However, additional proteins that coaccumulate in the detergent-insoluble AD brain proteome remain understudied. Here, we comprehensively characterized key proteins and pathways in the detergent-insoluble proteome from human AD brain samples using differential extraction, tandem mass tag (TMT) labeling, and two-dimensional LC-tandem mass spectrometry. To improve quantification accuracy of the TMT method, we developed a complement TMT-based strategy to correct for ratio compression. Through the meta-analysis of two independent detergent-insoluble AD proteome datasets (8914 and 8917 proteins), we identified 190 differentially expressed proteins in AD compared with control brains, highlighting the pathways of amyloid cascade, RNA splicing, endocytosis/exocytosis, protein degradation, and synaptic activity. To differentiate the truly detergent-insoluble proteins from copurified background during protein extraction, we analyzed the fold of enrichment for each protein by comparing the detergent-insoluble proteome with the whole proteome from the same AD samples. Among the 190 differentially expressed proteins, 84 (51%) proteins of the upregulated proteins (n = 165) were enriched in the insoluble proteome, whereas all downregulated proteins (n = 25) were not enriched, indicating that they were copurified components. The vast majority of these enriched 84 proteins harbor low-complexity regions in their sequences, including amyloid-β, Tau, TARDBP/TAR DNA-binding protein 43, SNRNP70/U1-70K, MDK, PTN, NTN1, NTN3, and SMOC1. Moreover, many of the enriched proteins in AD were validated in the detergent-insoluble proteome by five steps of differential extraction, proteomic analysis, or immunoblotting. Our study reveals a resource list of proteins and pathways that are exclusively present in the detergent-insoluble proteome, providing novel molecular insights to the formation of protein pathology in AD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.