ArticleMolecular neurodegeneration2018
Deep proteomic network analysis of Alzheimer's disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease.
Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 4 of them syntheses that pooled it.
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
145 citing papers in PubMed, 4 syntheses or guidelines pooled it, 256 citations in OpenAlex.
- Pooled it
- Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19-related gene for global cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Pooled it
- Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.Scientific data · 2021Pooled it
- Meta-Analysis of the Alzheimer's Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.Cell reports · 2020Pooled it
- Human iPSC models revealResearch square · 2026Article
- Integrative Transcriptomic Analysis Reveals Impaired Oligodendrocyte Maturation and Myelination Signature in the Hippocampus of a Murine Model of Neuropsychiatric Lupus.International journal of molecular sciences · 2026Article
- hypeR-GEM: connecting metabolite signatures to enzyme-coding genes via genome-scale metabolic models.Bioinformatics (Oxford, England) · 2026Article
- Integrated multi-omics analysis identifies potential therapeutic targets for Alzheimer's disease.Neural regeneration research · 2026Article
- Roles of RNA-Binding Nuclear Proteins in Alzheimer's Disease Pathophysiology.ACS pharmacology & translational science · 2026Review
- Identification of Alzheimer's disease subtypes and biomarkers from human multi-omics data using subspace merging algorithm.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.Molecular neurodegeneration · 2026Article
- hypeR-GEM: connecting metabolite signatures to enzyme-coding genes via genome-scale metabolic models.bioRxiv : the preprint server for biology · 2025Article
- Pharmacologic inhibition of PCBP2 biomolecular condensates relieves Alzheimer's disease.Nature communications · 2025Article
- Aβ Modulates Extracellular Vesicles Proteomic Profile Impacting Phosphorylation Mediators.Molecular neurobiology · 2025Article
- CSF Proteomics and Machine Learning Reveal Distinct Stages Across the Alzheimer's Disease Continuum.medRxiv : the preprint server for health sciences · 2025Article
- Region-specific proteomic analysis of aging rhesus macaques following chronic glutamate-carboxypeptidase-II (GCPII) inhibition elucidates potential treatment strategies for sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Proteomic Insight Into Alzheimer's Disease Pathogenesis Pathways.Proteomics · 2025Review
- Integrative brain omics approach highlights sn-1 lysophosphatidylethanolamine in Alzheimer's dementia.Nature communications · 2025Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe complicated cellular and biochemical changes that occur in brain during Alzheimer's disease are poorly understood. In a previous study we used an unbiased label-free quantitative mass spectrometry-based proteomic approach to analyze these changes at a systems level in post-mortem cortical tissue from patients with Alzheimer's disease (AD), asymptomatic Alzheimer's disease (AsymAD), and controls. We found modules of co-expressed proteins that correlated with AD phenotypes, some of which were enriched in proteins identified as risk factors for AD by genetic studies.
methodsThe amount of information that can be obtained from such systems-level proteomic analyses is critically dependent upon the number of proteins that can be quantified across a cohort. We report here a new proteomic systems-level analysis of AD brain based on 6,533 proteins measured across AD, AsymAD, and controls using an analysis pipeline consisting of isobaric tandem mass tag (TMT) mass spectrometry and offline prefractionation.
resultsOur new TMT pipeline allowed us to more than double the depth of brain proteome coverage. This increased depth of coverage greatly expanded the brain protein network to reveal new protein modules that correlated with disease and were unrelated to those identified in our previous network. Differential protein abundance analysis identified 350 proteins that had altered levels between AsymAD and AD not caused by changes in specific cell type abundance, potentially reflecting biochemical changes that are associated with cognitive decline in AD. RNA binding proteins emerged as a class of proteins altered between AsymAD and AD, and were enriched in network modules that correlated with AD pathology. We developed a proteogenomic approach to investigate RNA splicing events that may be altered by RNA binding protein changes in AD. The increased proteome depth afforded by our TMT pipeline allowed us to identify and quantify a large number of alternatively spliced protein isoforms in brain, including AD risk factors such as BIN1, PICALM, PTK2B, and FERMT2. Many of the new AD protein network modules were enriched in alternatively spliced proteins and correlated with molecular markers of AD pathology and cognition.
conclusionsFurther analysis of the AD brain proteome will continue to yield new insights into the biological basis of 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.