ArticleEMBO molecular medicine2018
A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.
Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- The contribution of brain banks to knowledge discovery in amyotrophic lateral sclerosis: A systematic review.Neuropathology and applied neurobiology · 2022Pooled it
- Advancement in therapeutic application of quantum dots in amyotrophic lateral sclerosis: current opportunities and challenges.Drug delivery and translational research · 2026Review
- Plasma Proteomic Signatures Predict Incident Amyotrophic Lateral Sclerosis: A Prospective Study Stratified by C9orf72 Expansion.Journal of cachexia, sarcopenia and muscle · 2026Article
- The Senescent Phenotype of Cultured Hypothalamic Astrocytes from Rats with Streptozotocin-Induced Dementia.Neurochemical research · 2026Article
- Intrathecal (GActa neuropathologica communications · 2026Article
- Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Emerging nano-derived therapy for the treatment of dementia: a comprehensive review.Drug delivery and translational research · 2026Review
- Intrathecal (GbioRxiv : the preprint server for biology · 2026Article
- Multi-platform integration of brain and CSF proteomes reveals biomarker panels for Alzheimer's disease.Briefings in bioinformatics · 2026Article
- Integrated multi-omics profiling reveals novel molecular biomarkers and pathways associated with Fragile X-associated tremor/ataxia syndrome.Frontiers in molecular neuroscience · 2026Article
- Synaptic changes contribute to persistent extra-motor behaviour deficits in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Review
- The FindMNDBiomarker Program: Protein Changes in Motor Neuron Disease/Amyotrophic Lateral Sclerosis Postmortem Tissue and Biofluids.Annals of neurology · 2025Article
- Proteomic analysis of brain and spinal cord tissue reveals distinct immune and mitochondrial processes between human and mouse ALS models.Scientific reports · 2025Article
- Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia.Molecular neurodegeneration · 2025Article
- TDP-43 pathology is associated with divergent protein profiles in ALS brain and spinal cord.Acta neuropathologica communications · 2025Article
- A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.Journal of neurochemistry · 2025Article
- Shared and disease-specific pathways in frontotemporal dementia and Alzheimer's and Parkinson's diseases.Nature medicine · 2025Article
- Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord.Acta neuropathologica · 2025Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
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Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlap in clinical presentation, neuropathology, and genetic underpinnings. The molecular basis for the overlap of these disorders is not well established. We performed a comparative unbiased mass spectrometry-based proteomic analysis of frontal cortical tissues from postmortem cases clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also included a subset of patients with the C9orf72 expansion mutation, the most common genetic cause of both ALS and FTD Our systems-level analysis of the brain proteome integrated both differential expression and co-expression approaches to assess the relationship of these differences to clinical and pathological phenotypes. Weighted co-expression network analysis revealed 15 modules of co-expressed proteins, eight of which were significantly different across the ALS-FTD disease spectrum. These included modules associated with RNA binding proteins, synaptic transmission, and inflammation with cell-type specificity that showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were also examined for their overlap with TDP-43 protein-protein interactions, revealing one module enriched with RNA-binding proteins and other causal ALS genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia. Together, these findings highlight the utility of integrative systems-level proteomic approaches to resolve clinical phenotypes and genetic mechanisms underlying the ALS-FTD disease spectrum in human brain.
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