ArticleMolecular neurodegeneration2025
Network analysis of the cerebrospinal fluid proteome reveals shared and unique differences between sporadic and familial forms of amyotrophic lateral sclerosis.
Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed.
- Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.Trends in cell biology · 2026Review
- Proteomic profile of CSF obtained at the time of diagnosis determines amyotrophic lateral sclerosis progression and survival: CXCL7 levels in disease prognosis and survival.Brain pathology (Zurich, Switzerland) · 2026Article
- The Target ALS Global Natural History Study: Cross-platform proteomics to accelerate biofluid biomarker and drug target discovery in amyotrophic lateral sclerosis.medRxiv : the preprint server for health sciences · 2026Article
- Associations between sleep disturbance and cerebrospinal fluid Aβ, and shared proteomic signatures in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Simultaneous profiling of native-state proteomes and transcriptomes of neural cell types using proximity labeling.Nature communications · 2026Article
- Decoding Neuroinflammatory Pathways: The Role of the CXCL12-CXCR4/CXCR7 Axis in ALS-Related Cognitive Impairment.Molecular neurobiology · 2026Review
- Decoding Dementia Mechanisms: Identification of Key Oligodendrocyte- Associated Genes through Integrative Bioinformatics and Machine Learning.Current topics in medicinal chemistry · 2026Article
- Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration.Nature aging · 2025Article
- ALS plasma biomarkers reveal neurofilament and pTau correlate with disease onset and progression.Annals of clinical and translational neurology · 2025Article
- SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.Acta neuropathologica · 2024Article
- SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.Research square · 2024Article
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25 authors.
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Abstract
backgroundAmyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3-5 years of disease onset. Although roughly 10% of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause(s) of most cases are unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups.
methodsWe employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from sporadic, C9orf72, and SOD1 ALS patients, asymptomatic C9orf72 expansion carriers, and controls (N = 101). To verify trends in our Emory University cohort we used data-independent acquisition (DIA-MS) on an expanded, four center cohort. This expanded cohort of 259 individuals included 50 sporadic ALS (sALS), 43 C9orf72 ALS, 22 SOD1 ALS, 72 asymptomatic gene carriers (59 C9orf72 and 13 SOD1) and 72 age-matched controls. We identified 2330 proteins and used differential protein abundance and network analyses to determine how protein profiles vary across disease subtypes in ALS CSF.
resultsDifferential abundance and co-expression network analysis identified proteomic differences between ALS and control, as well as differentially abundant proteins between sporadic, C9orf72 and SOD1 ALS. A panel of proteins differentiated forms of ALS that are indistinguishable in a clinical setting. An additional panel differentiated asymptomatic from symptomatic C9orf72 and SOD1 mutation carriers, marking a pre-symptomatic proteomic signature of genetic forms of ALS. Leveraging this large, multicenter cohort, we validated our ALS CSF network and identified ALS-specific proteins and network modules.
conclusionsThis study represents a comprehensive analysis of the CSF proteome across sporadic and genetic causes of ALS that resolves differences among these ALS subgroups and also identifies proteins that distinguish symptomatic from asymptomatic gene carriers. These new data point to varying pathogenic pathways that result in an otherwise clinically indistinguishable disease.
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