Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice
Abstract
Beta-amyloid (Aβ) plaques and chronic neuroinflammation are significant neuropathological features of Alzheimer's disease. Microglial cells in aged brains have potential to produce cytokines such as TNF and IL-1 family members (IL-1α, IL-1β, and IL-1Ra) and to phagocytose Aβ in Alzheimer's disease, however the inter-relationship between these processes is poorly understood. Here we show that % Aβ plaque load followed a sigmoidal trajectory with age in the neocortex of APPswe/PS1ΔE9 Tg mice, and correlated positively with soluble Aβ40 and Aβ42. Aβ measures were moderately correlated with mRNA levels of CD11b, TNF, and IL-1Ra. Cytokine production and Aβ load were assessed in neocortical CD11b(+)(CD45(+)) microglia by flow cytometry. Whereas most microglia in aged mice produced IL-1Ra, relatively low proportions of microglia produced TNF, IL-1α, and IL-1β. However, microglial production of these latter cytokines was generally increased in APP/PS1 Tg mice. Microglia that phagocytosed endogenously-produced Aβ were only observed in APP/PS1 Tg mice. Differences in phagocytic index and total Aβ load were observed in microglia with specific cytokine profiles. Both phagocytic index and total Aβ load were higher in IL-1α(+) and IL-1Ra(+) microglia, than microglia that did not produce these cytokines. In contrast, total Aβ load was lower in IL-1β(+) and TNF(+) microglia, compared to IL-1β(-) and TNF(-) microglia, and TNF(+) microglia also had a lower phagocytic index. Using GFP bone marr…
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This impairment has been shown to correlate with increased production of proinflammatory cytokines and overwhelming accumulation of Aβ plaques in the AD brain.
“This impairment has been shown to correlate with increased production of proinflammatory cytokines and overwhelming accumulation of Aβ plaques in the AD brain [20–22].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [20]
The findings are consistent with a study that found no change in Aβ phagocytosis in microglia producing IL-1β.
“These findings are consistent with a study that found no change in Aβ phagocytosis in microglia producing the cytokine IL-1β [20].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [20]
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- Authors
- Babcock, A. A., Ilkjær, L., Clausen, B. H., Villadsen, B., Dissing-Olesen, L., Bendixen, A. T. M., Lyck, L., Lambertsen, K. L., & Finsen, B.
- Affiliations
- University of Southern Denmark (DK)
- Corresponding author
- Babcock, Alicia A.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 48
- Pages
- 86-101
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2017615265
- Cited by
- 107
- References
- 25
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 10 · 2018: 14 · 2017: 7 · 2016: 10 · 2015: 6
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Funders
- Augustinus Foundation
- Aase og Ejnar Danielsens Fond
- Carl J. Beckers Fond
- The Carlsberg Foundation
- Frimodt-Heineke Fonden
- Grosserer M. Brogaard og Hustrus Mindefond
- Hørsløv Foundation
- Katrine og Vigo Skovgaards Fond
- Fonden til Lægevidenskabens Fremme
- The Lundbeck Foundation
- Frederik Dagnæs-Hansen
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Alzheimer's disease, amyloid plaques, microglia, cytokine production, neuroinflammation, APP/PS1 mice, aging, interleukin-1 receptor antagonist, IL-1β, TNF-α, IL-1α, microglial phagocytosis, bone marrow chimeric mice
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Mice, Transgenic, Cytokines, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Mice, Presenilin-1
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