ArticleNature medicine2025
Disruption of the cerebrospinal fluid-plasma protein balance in cognitive impairment and aging.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The trial behind it
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Who cites it
26 citing papers in PubMed.
- Evaluating the effects of aging on distribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Anti-CD320 Autoantibodies and Central Nervous System Vitamin B12 Deficiency in Idiopathic Myelopathy.JAMA neurology · 2026Article
- CSF fibrinogen predicts longitudinal Tau accumulation in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cross-disease LC-MS/MS plasma proteomics identifies reproducible shared and disease-enriched biomarker signatures in neurodegenerative disorders.Acta neuropathologica communications · 2026Article
- Preoperative Plasma and Cerebrospinal Fluid SNAP-25 Levels Predict Delayed Neurocognitive Recovery in Elderly Patients: A Prospective Observational Study.CNS neuroscience & therapeutics · 2026Observational
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Plasma proteomic signatures of early retinal neurodegeneration in diabetes: A multi-cohort study.PLoS medicine · 2026Observational
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
- Plasma proteomics reveals divergent sex-specific senescence and bone biology signatures across neurodegenerative diseases.bioRxiv : the preprint server for biology · 2026Article
- Therapeutic targeting of fibrin-microglia interactions ameliorates Alzheimer's disease-related hyperexcitability and brain network dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026Article
- Multiparametric CEST and Z-spectrum analysis proton (ZAP) as biomarkers of human brain aging.Scientific reports · 2026Article
- Circular RNAs in metabolic health: bridging the gap between molecular biology and therapy.Cell death & disease · 2026Review
- Shake and bake: a robust and cost-effective proteomic sample preparation workflow for plasma and cerebrospinal fluid.Clinical proteomics · 2026Article
- Choroid plexus organoids mimic amyloid uptake at the blood-cerebrospinal fluid-barrier.Frontiers in cellular neuroscience · 2026Article
- Identification of a robust multitarget protein panel for Parkinson's disease via absolute quantification and large-scale external replication.Brain communications · 2026Article
- Evaluating the effects of aging on biodistribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.bioRxiv : the preprint server for biology · 2025Article
- Development of a humanized anti-fibrin monoclonal antibody for the treatment of neuroinflammatory and retinal diseases.Journal of neuroinflammation · 2025Article
- Proteomic profiling of Alzheimer's disease and Vascular dementia reveals unique underlying signatures.medRxiv : the preprint server for health sciences · 2025Article
- Plasma-based brain age as a potential biomarker for cognitive health and risk of brain-related disorders.Communications medicine · 2025Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their transport across brain barriers. CSF to plasma ratios of 848 proteins increased with aging in healthy control individuals, including complement and coagulation proteins, chemokines and proteins linked to neurodegeneration, whereas 64 protein ratios decreased with age, suggesting substrate-specific barrier regulation. Notably, elevated CSF to plasma ratios of peripherally derived or vascular-associated proteins, including DCUN1D1, MFGE8 and VEGFA, were associated with preserved cognitive function. Genome-wide association studies identified genetic loci associated with CSF to plasma ratios of 241 proteins, many of which have known disease associations, including FCN2, the collagen-like domain of which may facilitate blood-CSF transport. Overall, this work provides molecular insight into the human brain barrier system and its disruption with age and disease, with implications for the development of brain-permeable therapeutics.
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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 Socratic graph.