ArticleStroke2023
Identification of Clinically Relevant Brain Endothelial Cell Biomarkers in Plasma.
Article in Stroke, 2023. 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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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- CMV titer associations with cognition and the plasma proteome implicate FLT1 and neurovascular mechanisms as potential moderators.Journal of neuroinflammation · 2026Article
- Multi-omics validation of myelin water fraction as a myelin-specific MRI biomarker.NeuroImage · 2026Article
- Multi-Omics Validation of Myelin Water Fraction as a Myelin-Specific MRI Biomarker.medRxiv : the preprint server for health sciences · 2025Article
- CD93 in Health and Disease: Bridging Physiological Functions and Clinical Applications.International journal of molecular sciences · 2025Review
- Benchmarking the AI-based diagnostic potential of plasma proteomics for neurodegenerative disease in 17,170 people.medRxiv : the preprint server for health sciences · 2025Article
- The secretome of senescent monocytes predicts age-related clinical outcomes in humans.Nature aging · 2025Article
- SomaScan Bioinformatics: Normalization, Quality Control, and Assessment of Pre-Analytical Variation.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Review
- Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Exploring Circulating Long Non-Coding RNAs in Mild Cognitive Impairment Patients' Blood.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundProteins expressed by brain endothelial cells (BECs), the primary cell type of the blood-brain barrier, may serve as sensitive plasma biomarkers for neurological and neurovascular conditions, including cerebral small vessel disease.
methodsUsing data from the BLSA (Baltimore Longitudinal Study of Aging; n=886; 2009-2020), BEC-enriched proteins were identified among 7268 plasma proteins (measured with SomaScanv4.1) using an automated annotation algorithm that filtered endothelial cell transcripts followed by cross-referencing with BEC-specific transcripts reported in single-cell RNA-sequencing studies. To identify BEC-enriched proteins in plasma most relevant to the maintenance of neurological and neurovascular health, we selected proteins significantly associated with 3T magnetic resonance imaging-defined white matter lesion volumes. We then examined how these candidate BEC biomarkers related to white matter lesion volumes, cerebral microhemorrhages, and lacunar infarcts in the ARIC study (Atherosclerosis Risk in Communities; US multisite; 1990-2017). Finally, we determined whether these candidate BEC biomarkers, when measured during midlife, were related to dementia risk over a 25-year follow-up period.
resultsOf the 28 proteins identified as BEC-enriched, 4 were significantly associated with white matter lesion volumes (CDH5 [cadherin 5], CD93 [cluster of differentiation 93], ICAM2 [intracellular adhesion molecule 2], GP1BB [glycoprotein 1b platelet subunit beta]), while another approached significance (RSPO3 [R-Spondin 3]). A composite score based on 3 of these BEC proteins accounted for 11% of variation in white matter lesion volumes in BLSA participants. We replicated the associations between the BEC composite score, CDH5, and RSPO3 with white matter lesion volumes in ARIC, and further demonstrated that the BEC composite score and RSPO3 were associated with the presence of ≥1 cerebral microhemorrhages. We also showed that the BEC composite score, CDH5, and RSPO3 were associated with 25-year dementia risk.
conclusionsIn addition to identifying BEC proteins in plasma that relate to cerebral small vessel disease and dementia risk, we developed a composite score of plasma BEC proteins that may be used to estimate blood-brain barrier integrity and risk for adverse neurovascular outcomes.
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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 OpenQuestion graph.