A deficiency in CCR2+ monocytes: the hidden side of Alzheimer’s disease
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by intracellular neurofibrillary tangle formation and extracellular amyloid-β (Aβ) deposition. To date, microglia seem to act as double-edged swords, being either beneficial (e.g. clearance of Aβ) or detrimental (e.g. secretion of neurotoxic factors) in AD. Following a rather intense debate on the question, a consensus has emerged that microglia can renew themselves via proliferation of already differentiated microglia as well as via the de novo recruitment of monocytes of mouse models of AD. However, recent advances suggest distinct function for resident and bone marrow-derived microglia (BMDM), and have emphasized the neuroprotective functions of BMDM. BMDM is the only subset of cells that restrict cerebral amyloidosis in the AD brain, which has been recently attributed to CCR2(+) monocytes. Moreover, an impaired recruitment of CCR2(+) monocytes has been reported in AD patients, as seen from the CCR2(+) monocytopenia found in the bloodstream and BM. The present review summarizes the current knowledge on the roles and dysfunctions of CCR2(+) monocytes in AD and their potential as key therapeutic targets.
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CCL2 has the known capacity to break down the blood brain barrier and recruit peripheral immune cells to sites of damage.
“consistent with the known capacity of CCL2 to break down the blood brain barrier and recruit peripheral immune cells to sites of damage.58–62”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [58]
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- Authors
- Naert, G., & Rivest, S.
- Affiliations
- Université Laval (CA)
- ORCID
- Rivest, Serge
- Venue
- Journal of Molecular Cell Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-07-26
- Volume
- 5
- Issue
- 5
- Pages
- 284-293
- ISSN
- 1674-2788 (ISSN-L)
- 1759-4685
- OpenAlex
- W2131196487
- Cited by
- 123
- References
- 25
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 3 · 2022: 9 · 2021: 23 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 12 · 2016: 12 · 2015: 14 · 2014: 3 · 2012: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Université Laval
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Alzheimer's disease, CCR2+ monocytes, microglia, amyloid-beta clearance, cerebral amyloidosis, monocyte recruitment, monocytopenia, neuroinflammation, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Monocytes, Microglia, Chemokine CCL2, Receptors, CCR2
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