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Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility
Published on: April 13, 2017
Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease
Alain R Simard1, Denis Soulet, Genevieve Gowing
1Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705 Laurier boul., Québec G1V 4G2, Canada.
Abstract:
Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques.
Insights
Bone marrow-derived microglia infiltrate Alzheimer's disease (AD) brain plaques, attracted by beta-amyloid. These cells efficiently clear amyloid deposits, suggesting a new therapeutic strategy for AD.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are the brain's resident immune cells.
- Alzheimer's disease (AD) is characterized by amyloid plaques.
- The role of peripheral immune cells in AD pathogenesis is under investigation.
Purpose of the Study:
- To investigate the origin and function of microglia within amyloid plaques in AD mouse models.
- To determine if blood-derived microglia can clear amyloid deposits.
Main Methods:
- Utilized transgenic mouse models of Alzheimer's disease.
- Observed microglial infiltration and morphology within amyloid plaques.
- Employed a novel AD transgenic mouse model expressing thymidine kinase under the CD11b promoter to distinguish blood-derived from resident microglia.
- Assessed the phagocytic capacity of different microglial populations for amyloid-beta.
Main Results:
- Massive infiltration of ramified and elongated microglia was observed in the core of amyloid plaques.
- A significant portion of these microglia originated from the bone marrow.
- Beta-amyloid-40 and -42 isoforms were identified as chemoattractants for these cells.
- Blood-derived microglia, unlike resident microglia, demonstrated efficient phagocytosis and elimination of amyloid deposits.
- These bone marrow-derived microglia effectively restricted amyloid deposition.
Conclusions:
- Recruitment of bone marrow-derived microglia is a key mechanism in managing amyloid pathology in AD.
- Targeting the chemoattraction and recruitment of these peripheral immune cells represents a promising therapeutic avenue for Alzheimer's disease.
- Enhancing the phagocytic activity of blood-derived microglia could be a powerful strategy for clearing toxic senile plaques.
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