Mechanisms of microglia accumulation in Alzheimer’s disease: therapeutic implications
Abstract
In Alzheimer's disease (AD), and other conditions affecting integrity of the blood-brain barrier, microglia can originate in the bone marrow, migrate into the blood and enter the brain in a chemokine-dependent manner. CCR2, a chemokine receptor that controls mononuclear phagocyte infiltration into the brain in multiple sclerosis, bacterial meningitis and neuropathic pain, also regulates microglia accumulation in mouse models of AD. CCR2 deficiency leads to lower microglia accumulation and higher brain beta-amyloid (Abeta) levels, indicating that early microglial accumulation promotes Abeta clearance. In support of this protective role, enhancing microglia accumulation delays progression of AD. AD mice that constitutively express interleukin-1 in the brain, or that are deficient in peripheral mononuclear phagocyte transforming growth factor-beta signaling, have increased microglia accumulation around beta-amyloid plaques and reduced AD-like pathology. Regulating microglia recruitment into the brain is a novel therapeutic strategy to delay or stop progression of AD. Here, we review the role of microglia in AD and the mechanisms of their accumulation and discuss implications for AD therapy.
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Microglia accumulation in 3D Aβ+ neurospheroids is consistent with previous findings in human AD brains and mouse models.
“the results were consistent with the previous findings in human AD brains and mouse models,45, 48”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [45]
In early AD, microglia migrate to Aβ plaques.
“In the early stage of AD, microglia migrate to Aβ plagues,45, 46”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [45]
Microglia form a protective barrier to protect brain tissue from the neurotoxicity of Aβ plaques.
“forming a protective barrier to protect brain tissue from the neurotoxicity of Aβ plaques”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [45]
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- Authors
- Khoury, J. E., & Luster, A. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Luster, Andrew D.
- ORCID
- Luster, Andrew D.
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 29
- Issue
- 12
- Pages
- 626-632
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W2117091440
- Cited by
- 171
- References
- 65
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 10 · 2014: 20 · 2013: 15 · 2012: 24
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS044973, NS059005, NS044973, R01NS059005)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Alzheimer's disease, CCR2, amyloid-beta clearance, amyloid plaques, interleukin-1, TGF-beta signaling, blood-brain barrier
- MeSH terms
- Alzheimer Disease, Animals, Bone Marrow Cells, Mice, Transgenic, Phagocytosis, Signal Transduction, Amyloid beta-Peptides, Microglia, Chemokines, Mice, Receptors, CCR2
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