Cited by 172Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsBarrier Structure and Function Studies

Mechanisms of microglia accumulation in Alzheimer’s disease: therapeutic implications

Khoury, Joseph El, Luster, Andrew D.·2008·Trends in Pharmacological Sciences

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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Registry

Crossref · 10.1016/j.tips.2008.08.004

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Authors
Khoury, J. E., & Luster, A. D.
Affiliations
Harvard University (US)
Corresponding author
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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