Distinct inflammatory phenotypes of microglia and monocyte‐derived macrophages in Alzheimer's disease models: effects of aging and amyloid pathology
Open accessAbstract
Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid‐β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte‐derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in Tg APP/PS 1 and Tg APP/PS 1dE9, two transgenic AD mouse models, compared to WT littermates. We only found MDM infiltration in very aged mice. We determined that MDM highly expressed activation markers at basal state. In contrast, microglia exhibited an activated phenotype only with normal aging and Aβ pathology. Our study showed that CD 14 and CD 36, two receptors involved in phagocytosis, were upregulated during Aβ pathogenesis. Moreover, we observed, at the protein levels in AD models, higher production of pro‐inflammatory mediators: IL‐1β, p40, iNOS, CCL‐3, CCL‐4, and CXCL‐1. Taken together, our data indicate that microglia and MDM display distinct phenotypes in AD models and highlight the specific effects of normal aging vs Aβ peptides on inflammatory processes that occur during the disease progression. These precise phenotypes of different subpopulations of myeloid cells in normal and pathologic conditions may allow the design of pertinent therapeutic strategy for AD.
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Accumulating evidence shows that microglia and monocytes play distinct roles in AD pathogenesis, thus implicating both the central and peripheral immune response in long-term outcome.
“Finally, accumulating evidence shows that microglia and monocytes play distinct roles in AD pathogenesis (116–119), thus implicating both the central and peripheral immune response in long-term outcome.”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [119]
Plaque-associated microglia contain intracellular Aβ, show proinflammatory morphological changes, and have increased proinflammatory markers including MHC II, CD36, IL-1, IL-6, and TNF.
“They contain intracellular Aβ, suggesting phagocytosis31, show proinflammatory morphological changes such as somatic swelling and process shortening (Fig. 2c), and have increased proinflammatory markers including major histocompatibility complex II, CD36, IL-1, IL-6, and TNF32,33.”
From Microglia in neurodegeneration (2018) · cites this paper as [33]
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- Authors
- Martin, E., Boucher, C., Fontaine, B., & Delarasse, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Delarasse, Cécile
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2016-10-08
- Volume
- 16
- Issue
- 1
- Pages
- 27-38
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5242297
- OpenAlex
- W2531162427
- Cited by
- 156
- References
- 40
- Citations by year
- 2026: 5 · 2025: 18 · 2024: 11 · 2023: 15 · 2022: 20 · 2021: 21 · 2020: 18 · 2019: 17 · 2018: 23 · 2017: 7 · 2016: 1
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- Association France Alzheimer
- 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, microglia, monocyte-derived macrophages, aging, amyloid-beta, neuroinflammation, myeloid cell activation, CD14, CD36, phagocytosis, inflammatory cytokines, chemokines, inducible nitric oxide synthase, IL-1β
- MeSH terms
- Aging, Alzheimer Disease, Animals, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Inflammation, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Monocytes, Phagocytosis, Phenotype, Amyloid beta-Peptides, Microglia, Chemokines, Lipopolysaccharide Receptors, CD36 Antigens, Myeloid Cells, Nitric Oxide Synthase Type II, Plaque, Amyloid
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