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Updated: May 10, 2026
Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model
Published on: July 26, 2011
Peripheral monocyte-derived cells counter amyloid plaque pathogenesis in a mouse model of Alzheimer's disease
Ping Yan1,2, Ki-Wook Kim3,4, Qingli Xiao1,2
1Department of Neurology.
Abstract:
Microglia, the parenchymal tissue macrophages in the brain, surround amyloid plaques in brains of individuals with Alzheimer's disease (AD) but are ineffective at clearing amyloid to mitigate disease progression. Recent studies in mice indicate that microglia are derived exclusively from primitive yolk sac hematopoiesis and self-renew without contribution from ontogenically distinct monocytes/macrophages of definitive adult hematopoietic origin. Using a genetic fate-mapping approach to label cells of definitive hematopoietic origin throughout life span, we discovered that circulating monocytes contribute 6% of plaque-associated macrophages in aged AD mice. Moreover, peripheral monocytes contributed to a higher fraction of macrophages in the choroid plexus, meninges, and perivascular spaces of aged AD mice versus WT control mice, indicating enrichment at potential sites for entry into the brain parenchyma. Splenectomy, which markedly reduced circulating Ly6Chi monocytes, also reduced abundance of plaque-associated macrophages of definitive hematopoietic origin, resulting in increased amyloid plaque load. Together, these results indicate that peripherally derived monocytes invade the brain parenchyma, targeting amyloid plaques to reduce plaque load.
Insights
Peripherally derived monocytes can enter the brain and target amyloid plaques in Alzheimer's disease (AD). Reducing these monocytes increases amyloid plaque load, suggesting a therapeutic role for peripheral monocytes in AD.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia, brain macrophages, surround but fail to clear amyloid plaques in Alzheimer's disease (AD).
- Previous research suggested microglia exclusively originate from yolk sac hematopoiesis, excluding adult monocyte contribution.
Purpose of the Study:
- To investigate the contribution of circulating monocytes to brain macrophages in aged AD mouse models.
- To determine if peripheral monocytes target amyloid plaques and influence AD pathology.
Main Methods:
- Employed a genetic fate-mapping technique to trace cells of definitive hematopoietic origin throughout the lifespan.
- Utilized splenectomy to reduce circulating monocytes and assessed its impact on plaque-associated macrophages and amyloid plaque load.
Main Results:
- Circulating monocytes were found to constitute 6% of plaque-associated macrophages in aged AD mice.
- Peripheral monocytes were enriched in brain entry sites (choroid plexus, meninges, perivascular spaces) of aged AD mice compared to controls.
- Splenectomy reduced definitive hematopoietic-derived macrophages and increased amyloid plaque load.
Conclusions:
- Peripherally derived monocytes infiltrate the brain parenchyma and target amyloid plaques.
- These infiltrating monocytes play a role in reducing amyloid plaque burden in AD.
- Peripheral monocyte contribution to brain macrophages is significant in AD pathogenesis.
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