Microglial Uptake of Extracellular Tau by Actin-Mediated Phagocytosis

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Microglia act as the brain's primary immune cells, clearing cellular debris and pathogens.
• In Alzheimer's disease, microglia are implicated in clearing pathological protein aggregates like Amyloid-β and Tau.
• Understanding Tau internalization by microglia is crucial for developing Alzheimer's disease therapeutics.

Purpose of the Study:

• To visualize and characterize the phagocytic structures involved in microglial uptake of extracellular Tau species.
• To elucidate the molecular mechanisms underlying Tau phagocytosis by microglia.

Main Methods:

• Wide-field fluorescence microscopy
• Confocal microscopy
• 3D reconstruction and visualization of phagocytic structures

Main Results:

• Visualized microglia forming actin-rich, cup-like extensions to surround extracellular Tau.
• Demonstrated the association of filamentous actin with Tau phagocytosis.
• Observed the co-assembly of LC-3 molecules with phagosomes during Tau internalization.

Conclusions:

• Microglia utilize specific actin-dependent phagocytic structures to internalize extracellular Tau.
• The process involves the recruitment of LC-3 to phagosomes, suggesting autophagosome involvement.
• Detailed visualization provides insights into the cellular mechanisms of Tau clearance in neurodegenerative diseases.