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Updated: Dec 30, 2025
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Plaque-associated myeloid cells derive from resident microglia in an Alzheimer's disease model
Erin G Reed-Geaghan1, Andrew L Croxford2, Burkhard Becher2
1Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH.
Abstract:
Alzheimer's disease (AD) is accompanied by a robust inflammatory response mediated by plaque-associated myeloid cells of the brain. These cells exhibit altered gene expression profiles and serve as a barrier, preventing neuritic dystrophy. The origin of these cells has been controversial and is of therapeutic importance. Here, we genetically labeled different myeloid populations and unequivocally demonstrated that plaque-associated myeloid cells in the AD brain are derived exclusively from resident microglia, with no contribution from circulating peripheral monocytes.
Insights
Alzheimer's disease involves brain inflammation from myeloid cells. This study proves these cells originate solely from resident microglia, not circulating monocytes, offering therapeutic insights.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Alzheimer's disease (AD) features brain inflammation driven by myeloid cells near amyloid plaques.
- These plaque-associated myeloid cells display altered gene expression and protect against neuritic dystrophy.
- The cellular origin of these myeloid cells in AD is critical for developing targeted therapies.
Purpose of the Study:
- To definitively determine the origin of myeloid cells associated with amyloid plaques in the Alzheimer's disease brain.
- To investigate whether circulating peripheral monocytes contribute to the myeloid cell population at plaque sites.
Main Methods:
- Utilized genetic labeling techniques to trace the lineage of myeloid cell populations within the brain.
- Distinguished between resident microglia and infiltrating peripheral monocytes in an Alzheimer's disease model.
Main Results:
- Unequivocally demonstrated that all plaque-associated myeloid cells in the AD brain are derived from resident microglia.
- Confirmed a complete absence of contribution from circulating peripheral monocytes to these plaque-associated myeloid cells.
Conclusions:
- Resident microglia are the exclusive source of myeloid cells at amyloid plaques in Alzheimer's disease.
- This finding clarifies a long-standing controversy and has significant implications for AD-targeted immunotherapies.
