The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology
Open accessAbstract
We hypothesize that microglial chemotactic responses to amyloid-β peptide (Aβ 1–42) serve as an early and integral component of inflammatory response in Alzheimer's disease (AD) brain. This study reports a receptor for vascular endothelial growth factor (VEGF), termed VEGF-1 (Flt-1), subserves microglial chemotactic responses induced by Aβ 1–42 stimulation,in vivo and in vitro. Expression of Flt-1 was significantly increased in tissue obtained from AD patients [compared with tissue from nondemented (ND) individuals], in Aβ 1–42-injected rat hippocampus, and in peptide-stimulated human microglia. Single and double immunohistochemical staining demonstrated marked immunoreactivity, for both Flt-1 and its ligand VEGF, in association with microglia and Aβ deposits in AD, but not ND, brain tissue. Functionally, treatment with anti-Flt-1 antibody was highly effective in inhibiting microglial mobility and chemotactic responses measured in vitro using a transwell migration assay.In vivo, transplanted enhanced green fluorescent protein (EGFP)-labeled microglia exhibited Flt-1-dependent chemotaxis induced by peptide injection with anti-Flt-1 effective in blocking migration of cells. Importantly, anti-Flt-1 reduction of microglial mobility was neuroprotective in peptide-injected hippocampus and associated with a significant increase in numbers of viable hippocampal neurons. The results of this study suggest critical functional roles for Flt-1 in mediating microglial chemotactic inflammatory responses which contribute to pathological conditions in AD brain.
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“Interestingly, upregulation of Flt-1 has been observed in the entorhinal cortical sections from human AD brain and in human microglia cells following treatment with Aβ42.36”
From CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease (2018) · cites this paper as [36]
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“The growth factor VEGF, along with its receptor Flt-1, which is expressed on microglia, has also been implicated in the microglial chemotactic response to Aβ deposits through both in vitro and in vivo experiments [86].”
From Microglial dysfunction in brain aging and Alzheimer's disease (2014) · cites this paper as [86]
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Cites
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Self-citation
Metadata
- Authors
- Ryu, J. K., Cho, T., Choi, H. B., Wang, Y. T., & McLarnon, J. G.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- McLarnon, James G.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-01-07
- Volume
- 29
- Issue
- 1
- Pages
- 3-13
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6664925
- OpenAlex
- W2022811766
- Cited by
- 121
- References
- 45
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 12 · 2023: 10 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 1 · 2015: 9 · 2014: 6 · 2013: 13 · 2012: 8
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Fondation pour la Recherche sur Alzheimer
- Department of Psychiatry, Faculty of Medicine, University of British Columbia
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, microglia, amyloid-beta, microglial chemotaxis, neuroinflammation, microglial migration, neuroprotection, hippocampus, amyloid-beta deposition
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Animals, Cell Movement, Cells, Cultured, Disease Models, Animal, Glial Fibrillary Acidic Protein, Hippocampus, HLA-DR Antigens, Humans, Mice, Transgenic, Middle Aged, Peptide Fragments, Phosphopyruvate Hydratase, Postmortem Changes, RNA, Messenger, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Microglia, Entorhinal Cortex, CD11b Antigen, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor-1, Green Fluorescent Proteins, Mice, Rats
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