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Updated: May 16, 2026
Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease
Published on: July 6, 2019
Effective targeting of Aβ to macrophages by sonochemically prepared surface-modified protein microspheres
Michal Richman1, Alex Perelman, Asaf Gertler
1Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
Abstract:
Imbalanced homeostasis and oligomerization of the amyloid-β (Aβ) peptide in the brain are hallmarks of Alzheimer's disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing Aβ from the brain or inducing inflammation. Recent evidence suggests that clearance of Aβ by microglia/macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of Aβ in the brain. We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an Aβ-recognition motif can strongly bind Aβ, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium. Here, we describe how microsphere-bound Aβ can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of Aβ removal and, thus, contribute to the clearance of Aβ, even by defective microglial cells. The phagocytosis was most effective, with microspheres having a diameter of <1 μm. The introduction of polyethylene glycol to the surface of the microspheres changed the kinetics of the phagocytosis. Moreover, while aggregated Aβ induced a significant inflammatory response that was manifested by the release of TNF-α, the microsphere-bound Aβ dramatically reduced the amount of cytokine released from microglial cells.
Insights
Protein microspheres can bind amyloid-beta (Aβ) and promote its clearance by microglial cells, even those defective in Alzheimer's disease (AD). This approach reduces Aβ toxicity and inflammation, offering a novel therapeutic strategy for AD.
Area of Science:
- Neuroscience
- Biomaterials Science
- Immunology
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) peptide aggregation and impaired Aβ clearance by microglia.
- Microglial dysfunction in Aβ clearance contributes to AD pathogenesis.
- Previous work showed Aβ-binding microspheres inhibit Aβ aggregation and toxicity.
Purpose of the Study:
- To investigate if microsphere-bound Aβ can be phagocytosed by microglia.
- To determine if this phagocytosis mechanism can clear Aβ, even in defective microglia.
- To assess the impact of microsphere-bound Aβ on microglial inflammatory responses.
Main Methods:
- Protein microspheres functionalized with Aβ-recognition motifs were used.
- Phagocytosis of microsphere-bound Aβ by microglial cells was analyzed.
- The effect of microsphere size and surface modification (e.g., polyethylene glycol) on phagocytosis was studied.
- Tumor necrosis factor-alpha (TNF-α) release from microglia was measured.
Main Results:
- Microsphere-bound Aβ stimulated microglial phagocytosis via a novel mechanism.
- Effective Aβ clearance was observed even in microglia with defective Aβ removal pathways.
- Phagocytosis efficiency was highest for microspheres <1 μm in diameter.
- Surface modification with polyethylene glycol altered phagocytosis kinetics.
- Microsphere-bound Aβ significantly reduced inflammatory cytokine release (TNF-α) compared to aggregated Aβ.
Conclusions:
- Microsphere-bound Aβ can be effectively phagocytosed by microglia, facilitating Aβ clearance.
- This strategy bypasses defective microglial pathways in AD, offering therapeutic potential.
- Microsphere-bound Aβ exhibits reduced inflammatory potential compared to aggregated Aβ.
