ArticleThe Journal of experimental medicine2022
A "multi-omics" analysis of blood-brain barrier and synaptic dysfunction in APOE4 mice.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Impact of Apolipoprotein E4 on blood-brain barrier integrity in target replacement murine models: a systematic review and meta-analysis.Alzheimer's research & therapy · 2026Pooled it
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Protocol for isolation of the brain vasculature from the mouse cortex for proteomics.STAR protocols · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- From cooperation to collapse: the diet-microbiota-host gene triad in disease and aging.Frontiers in microbiomes · 2026Review
- APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice.Neurobiology of disease · 2026Article
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk.Nature communications · 2025Article
- ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells.Stem cell reports · 2025Article
- Review
- Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions.Acta pharmaceutica Sinica. B · 2025Review
- Alzheimer's disease pathogenesis: standing at the crossroad of lipid metabolism and immune response.Molecular neurodegeneration · 2025Review
- Krüppel-like factor 4 transcription factor in blood-brain barrier endothelial cells: A potential role in Alzheimer's disease.Animal models and experimental medicine · 2025Review
- Pericytes in the Development and Progression of Brain Diseases.Aging and disease · 2025Review
- A molecular brain atlas reveals cellular shifts during the repair phase of stroke.Journal of neuroinflammation · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer's Disease.Cells · 2025Review
- Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.Molecular neurodegeneration · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein E4 (APOE4), the main susceptibility gene for Alzheimer's disease, leads to blood-brain barrier (BBB) breakdown in humans and mice. Remarkably, BBB dysfunction predicts cognitive decline and precedes synaptic deficits in APOE4 human carriers. How APOE4 affects BBB and synaptic function at a molecular level, however, remains elusive. Using single-nucleus RNA-sequencing and phosphoproteome and proteome analysis, we show that APOE4 compared with APOE3 leads to an early disruption of the BBB transcriptome in 2-3-mo-old APOE4 knock-in mice, followed by dysregulation in protein signaling networks controlling cell junctions, cytoskeleton, clathrin-mediated transport, and translation in brain endothelium, as well as transcription and RNA splicing suggestive of DNA damage in pericytes. Changes in BBB signaling mechanisms paralleled an early, progressive BBB breakdown and loss of pericytes, which preceded postsynaptic interactome disruption and behavioral deficits that developed 2-5 mo later. Thus, dysregulated signaling mechanisms in endothelium and pericytes in APOE4 mice reflect a molecular signature of a progressive BBB failure preceding changes in synaptic function and behavior.
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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.