Cited by 124Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

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Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology

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Ryu, Jae K., Cho, Taesup, Choi, Hyun B., Wang, Yu Tian, McLarnon, James G.·2009·The Journal of Neuroscience

DOI 10.1523/jneurosci.2888-08.2009PMC PMC6664925

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Abstract

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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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.
ORCID: Ryu, Jae K.
Choi, Hyun B.
Wang, Yu Tian
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
DOI: 10.1523/jneurosci.2888-08.2009
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
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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Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology

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