ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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
13 citing papers in PubMed, 14 citations in OpenAlex.
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Proteomic signatures of protected APOE ε4 carriers reveal causal pathways associated with delayed Alzheimer's disease onset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Proteomic Signatures of ProtectedmedRxiv : the preprint server for health sciences · 2026Article
- Neurexins, Ephrin receptors, and N-cadherin signaling as emerging mechanisms in synaptic dysfunction and neurodegenerative diseases.Communications biology · 2026Review
- Deciphering the Impact of EPHA1-AS1 Gene Polymorphism on Social Cognition Deficits in Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- The immune-endothelial axis in neurovascular pathophysiology: a framework for targeted interventions.Frontiers in immunology · 2026Review
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- PreoperativeFrontiers in bioinformatics · 2026Review
- Chimeric Antigen Receptor Cell Therapy: Current Status and Its Potential in Aging and Alzheimer's Disease.International journal of molecular sciences · 2025Review
- A List-Based Parallel Bacterial Foraging Algorithm for the Multiple Sequence Alignment Problem.Biomimetics (Basel, Switzerland) · 2025Article
- Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis.Frontiers in pharmacology · 2025Article
- Tracking neuroinflammatory biomarkers in Alzheimer's disease: a strategy for individualized therapeutic approaches?Journal of neuroinflammation · 2024Review
- Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionGenome-wide association studies link susceptibility to late-onset Alzheimer's disease (LOAD) with EphA1. Sequencing identified a non-synonymous substitution P460L as a LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that P460L dysregulates EphA1 receptor activity and impacts neuroinflammation.
methodsEphA1/P460L receptor activity was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble EphA1/P460L (sEphA1/sP460L) reverse signaling in brain endothelial cells was assessed by T-cell recruitment and barrier function assays.
resultsEphA1 and P460L were expressed in HEK cells, but membrane and soluble P460L were significantly reduced. Ligand engagement induced Y781 phosphorylation of EphA1 but not P460L. sEphA1 primed brain endothelial cells for increased T-cell recruitment; however, sP460L was less effective. sEphA1 decreased the integrity of the brain endothelial barrier, while sP460L had no effect. DISCUSSION: These findings suggest that P460L alters EphA1-dependent forward and reverse signaling, which may impact blood-brain barrier function in LOAD. HIGHLIGHTS: EphA1-dependent reverse signaling controls recruitment of T cells by brain endothelial cells. EphA1-dependent reverse signaling remodels brain endothelial cell contacts. LOAD-associated P460L variant of EphA1 shows reduced membrane expression and reduced ligand responses. LOAD-associated P460L variant of EphA1 fails to reverse signal to brain endothelial cells.
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.