Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Aβ...

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Amyloid-beta (Aβ) plaques are a hallmark of Alzheimer's disease (AD).
• Microglia, the brain's immune cells, use complement receptors to clear pathogens.
• Complement component C3 and complement receptor type 3 (CR3, Mac-1) are implicated in microglial phagocytosis.

Purpose of the Study:

• To investigate the role of complement component C3 and Mac-1 in the phagocytosis and clearance of fibrillar amyloid-beta (fAβ) by microglia.
• To provide direct evidence for C3 and Mac-1 mediating fAβ clearance in vitro and in vivo.

Main Methods:

• Murine microglia were used for in vitro phagocytosis assays with synthetic fAβ(42) and patient-derived amyloid cores.
• Knockdown or deficiency of C3 or Mac-1 was employed to assess their impact on fAβ uptake.
• In vivo studies involved microinjection of fluorescent fAβ(42) into wild-type and C3/Mac-1 knockout mice.

Main Results:

• Microglia demonstrated uptake of synthetic fAβ(42) and patient amyloid cores, with lysosomal transport observed.
• Deficiency or knockdown of C3 or Mac-1 significantly reduced fAβ uptake.
• In vivo, reduced clearance of fAβ was observed in C3 and Mac-1 knockout mice compared to wild-type controls.

Conclusions:

• Complement component C3 and Mac-1 play a partial role in the phagocytosis and clearance of fibrillar amyloid-beta by microglia.
• These findings support a potentially beneficial role for microglia and the complement system in Alzheimer's disease pathogenesis.