ArticlePloS one2011
Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer's disease.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
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Who cites it
166 citing papers in PubMed, 289 citations in OpenAlex.
- The Roles of Transcription Factor Ets-1 in Neurological Disorders.Molecular neurobiology · 2026Review
- Peptide-Functionalized Hydroxypropyl Cellulose Mitigates Amyloid-β Protein Induced Endothelial Leakiness and Enhances Cognitive Function in Alzheimer's Disease.Angewandte Chemie (International ed. in English) · 2026Article
- Cerebrovascular Single-Nucleus RNA-Seq Reveals Heat Shock Activation and Vascular Remodeling in Alzheimer's Disease and Primary Tauopathies.Research square · 2026Article
- Choroidal Changes in Cerebral Amyloid Angiopathy Studied by Optical Coherence Tomography Angiography.Translational stroke research · 2026Article
- Dysfunction of the neurovascular unit as a temporal driver in Alzheimer's pathogenesis.Translational neurodegeneration · 2026Review
- Obesity as a catalyst for neurodegeneration.Nature metabolism · 2026Review
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
- APPswe mutation causes functional deficits in endothelial cells generated by transient ETV2 overexpression in human iPSCs.Fluids and barriers of the CNS · 2025Article
- Cerebrovascular protective functions of amyloid precursor protein: Progress and therapeutic prospects.Pharmacology & therapeutics · 2025Review
- Assessing blood-brain barrier (BBB) integrity in an Alzheimer's disease mouse model: is the BBB globally or locally disrupted?Fluids and barriers of the CNS · 2025Article
- Blockade of AGeroScience · 2025Article
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Functionally distinct pericyte subsets differently regulate amyloid-β deposition in patients with Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2025Article
- Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.Biomaterials · 2025Article
- Ferric Ammonium Citrate Reduces Claudin-5 Abundance and Function in Primary Mouse Brain Endothelial Cells.Pharmaceutical research · 2025Article
- Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.Cell death & disease · 2025Article
- Optical attenuation coefficient decorrelation-based optical coherence tomography angiography for microvascular evaluation of Alzheimer's disease on mice.Neurophotonics · 2025Article
- Subpopulation Alterations of Vascular Endothelial Cells in the Cerebral Cortex in Experimental Models of Alzheimer's Disease.Bulletin of experimental biology and medicine · 2025Article
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
106 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the "Vascular hypothesis", holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes early-onset AD. The expression of tight junction (TJ) proteins, occludin and ZO-1, were examined in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes, was directly linked to an increased microvascular density but not apoptosis, which strongly supports amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration.
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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.