ArticleBrain : a journal of neurology2022
Activation of Wnt/β-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 2 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 2 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Unlocking the secrets of NPSLE: the role of dendritic cell-secreted CCL2 in blood-brain barrier disruption.Frontiers in immunology · 2024Pooled it
- Pooled it
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- Mechanisms of electroacupuncture for the treatment of Alzheimer's disease by activating Wnt/β-catenin pathway to improve blood-brain barrier function.IBRO neuroscience reports · 2026Article
- Role of the Blood-Brain Barrier in the Pathophysiology of Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A Comparative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Baicalin and CNS-related diseases: new insights into neuroprotective potentials based on underlying mechanisms.Biochemistry and biophysics reports · 2026Review
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Serotonergic System Dysregulation in Alzheimer's Disease.ACS chemical neuroscience · 2026Review
- GPR146 Deficiency Enhances Microglial Phagocytosis and Blood-Brain Barrier-Associated Markers in an Acute Amyloid-β Model.Molecular neurobiology · 2026Article
- Review
- The Exercise-CTSS-AD Axis: a novel framework for understanding exercise-induced neuroprotection in Alzheimer's disease.Metabolic brain disease · 2026Review
- Mapping cross-domain drivers of Alzheimer's disease risk through integrated network analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Fecal miRNome and Proteome Profiling Uncovers Stage-Specific Biomarkers of Alzheimer's Disease in 3×Tg-AD Mice.Cellular and molecular neurobiology · 2026Article
- Spatial-temporal lipidomics reveals dysregulated lipid metabolism in mouse brain during Alzheimer's disease progression.Journal of advanced research · 2026Article
- Accelerated reprogramming of hiPSCs into functional brain endothelial-like cells using multiplexed CRISPR activation.Scientific reports · 2026Article
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- Dysfunctional astrocytes regulate excitatory neurons via cell adhesion and vascular lesions in patients with Alzheimer's disease.Journal of translational medicine · 2026Article
- Review
- Plasma miRNAs associated with cognitive impairment and brain hypometabolism in individuals with mild cognitive impairment.BMC neurology · 2026Article
- ISX9 activates the Wnt/β-catenin signaling pathway and exerts neuroprotective effects in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 5 countries.
Funding
Abstract
Alzheimer's disease is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for Alzheimer's disease pose a significant challenge, because the mechanisms of disease are not being fully understood. Malfunction of the blood-brain barrier is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease, especially at the early stages of the disease. However, the underlying mechanisms remain poorly characterized, while few molecules can directly target and improve blood-brain barrier function in the context of Alzheimer's disease. Here, we showed dysfunctional blood-brain barrier in patients with Alzheimer's disease reflected by perivascular accumulation of blood-derived fibrinogen in the hippocampus and cortex, accompanied by decreased tight junction proteins Claudin-5 and glucose transporter Glut-1 in the brain endothelial cells. In the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, blood-brain barrier dysfunction started at 4 months of age and became severe at 9 months of age. In the cerebral microvessels of APP/PS1 mice and amyloid-β-treated brain endothelial cells, we found suppressed Wnt/β-catenin signalling triggered by an increase of GSK3β activation, but not an inhibition of the AKT pathway or switching to the Wnt/planar cell polarity pathway. Furthermore, using our newly developed optogenetic tool for controlled regulation of LRP6 (upstream regulator of the Wnt signalling) to activate Wnt/β-catenin pathway, blood-brain barrier malfunction was restored by preventing amyloid-β-induced brain endothelial cells impairments and promoting the barrier repair. In conclusion, targeting LRP6 in the Wnt/β-catenin pathway in the brain endothelium can alleviate blood-brain barrier malfunction induced by amyloid-β, which may be a potential treatment strategy for Alzheimer's disease.
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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.