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Updated: May 20, 2026
Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
The neuroimmune system in Alzheimer's disease: the glass is half full
Suzanne E Hickman1, Joseph El Khoury
1Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Abstract:
It is well established that microglia, the neuroimmune cells of the brain, are associated with amyloid-β (Aβ) deposits in Alzheimer's disease (AD). However, the roles of these cells and other mononuclear phagocytes such as monocytes and macrophages in AD pathogenesis and progression have been elusive. Clues to mononuclear phagocyte involvement came with the demonstration that Aβ directly activates microglia and monocytes to produce neurotoxins, signifying that a receptor mediated interaction of Aβ with these cells may be critical for neurodegeneration seen in AD. Also, in AD brain, mononuclear phagocyte distribution changes from a uniform pattern that covers the brain parenchyma to distinct clusters intimately associated with areas of Aβ deposition, but the driving force behind this choreography was unclear. Here, we review our recent work identifying mononuclear phagocyte receptors for Aβ and unraveling mechanisms of recruitment of these cells to areas of Aβ deposition. While our findings and those of others have added significantly to our understanding of the role of the neuroimmune system in AD, the glass remains half full (or half empty) and a lot remains to be uncovered.
Insights
Microglia and other immune cells in Alzheimer's disease (AD) interact with amyloid-β (Aβ) plaques. Identifying receptors and recruitment mechanisms is key to understanding neuroinflammation and AD progression.
Area of Science:
- Neuroimmunology
- Alzheimer's Disease Pathogenesis
Background:
- Microglia, the brain's immune cells, are linked to amyloid-β (Aβ) in Alzheimer's disease (AD).
- The specific roles of microglia, monocytes, and macrophages in AD progression remain unclear.
- Aβ activates microglia and monocytes, suggesting receptor-mediated interactions are crucial for neurodegeneration.
Purpose of the Study:
- To review recent findings on mononuclear phagocyte receptors for Aβ.
- To elucidate mechanisms of mononuclear phagocyte recruitment to Aβ deposits.
- To advance understanding of the neuroimmune system's role in AD.
Main Methods:
- Review of recent research on mononuclear phagocyte-Aβ interactions.
- Identification of specific receptors mediating Aβ recognition by immune cells.
- Investigation of cellular recruitment mechanisms to amyloid pathology.
Main Results:
- Mononuclear phagocyte receptors for Aβ have been identified.
- Mechanisms driving the recruitment of these cells to Aβ deposition sites are being unraveled.
- Evidence suggests Aβ directly activates immune cells, contributing to neuroinflammation.
Conclusions:
- Significant progress has been made in understanding the neuroimmune system's involvement in AD.
- Further research is needed to fully elucidate the complex roles of immune cells in AD pathogenesis.
- Identifying Aβ-receptor interactions and recruitment pathways offers potential therapeutic targets.
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