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Cited by 114Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and Treatments

CCL2 Accelerates Microglia-Mediated Aβ Oligomer Formation and Progression of Neurocognitive Dysfunction

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Kiyota, Tomomi, Yamamoto, Masaru, Xiong, Huangui, Lambert, Mary P., Klein, William L., Gendelman, Howard E., Ransohoff, Richard M., Ikezu, Tsuneya·2009·PLoS ONE
DOI 10.1371/journal.pone.0006197PMC PMC2703798
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Abstract

BACKGROUND: The linkages between neuroinflammation and Alzheimer's disease (AD) pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish beta-amyloid (Abeta) precursor protein mutant. METHODOLOGY/PRINCIPAL FINDINGS: We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in beta-amyloid precursor protein (APP) mice as early as 2-3 months of age. This is followed by increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2 does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha directly facilitated Abeta uptake, intracellular Abeta oligomerization, and protein secretion. CONCLUSIONS/SIGNIFICANCE: We posit that CCL2 facilitates Abeta oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Abeta seeding in the brain.

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References 45 · Cited by 114

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Authors
Kiyota, T., Yamamoto, M., Xiong, H., Lambert, M. P., Klein, W. L., Gendelman, H. E., Ransohoff, R. M., & Ikezu, T.
Affiliations
  • University of Nebraska Medical Center (US)
  • Northwestern University (US)
  • Cleveland Clinic (US)
Corresponding author
Ikezu, Tsuneya
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-07-10
Volume
4
Issue
7
Pages
e6197
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0006197
PMC
PMC2703798
OpenAlex
W2033369082
Cited by
114
References
45
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 4 · 2020: 5 · 2019: 10 · 2018: 3 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 8
FWCI
4.65
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institutes of Health (R37 NS36126, NS043985)
  • National Institute on Aging (R21AG032600)
  • National Institute of Neurological Disorders and Stroke (R37NS036126, R37 NS36126, R01NS32151, R01NS032151, P01NS043985)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
MCP-1, microglia, amyloid-beta oligomers, Alzheimer's disease, neuroinflammation, microglial activation, neurocognitive impairment, spatial memory, working memory, hippocampal synaptic transmission, APP transgenic mice, TNF-α, amyloid-beta uptake, Tg2576 mice
MeSH terms
Animals, Biopolymers, Cognition Disorders, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Memory Disorders, Mice, Transgenic, Tumor Necrosis Factor-alpha, Blotting, Western, Amyloid beta-Peptides, Microglia, Chemokine CCL2, Mice

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