Microglial phagocytosis in Alzheimer disease

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Alzheimer disease (AD) pathogenesis is increasingly linked to microglial phagocytosis dysregulation.
• Ageing exacerbates AD risk by impairing microglial amyloid-β (Aβ) plaque clearance while promoting neuronal and synaptic engulfment.

Purpose of the Study:

• To elucidate the multifaceted roles of microglial phagocytosis in Alzheimer disease (AD).
• To highlight the genetic links between microglial phagocytosis and AD risk.
• To explore the therapeutic potential of modulating microglial phagocytosis in AD.

Main Methods:

• Review of accumulating evidence on microglial phagocytosis in AD.
• Analysis of genetic risk factors associated with microglial phagocytosis in AD.
• Evaluation of current disease-modifying treatments targeting microglial phagocytosis.

Main Results:

• Numerous AD genetic risk factors directly implicate microglial phagocytosis pathways.
• Anti-amyloid-β (Aβ) antibodies, a disease-modifying AD treatment, enhance microglial Aβ phagocytosis.
• Microglial phagocytosis of Aβ appears beneficial by reducing plaques and tau pathology, while synaptic phagocytosis may be detrimental in later AD stages.

Conclusions:

• Microglial phagocytosis plays a complex, dual role in Alzheimer disease (AD) progression.
• Targeting microglial phagocytosis pathways offers potential for novel AD therapeutics.
• Further research into the intricate mechanisms of microglial phagocytosis is crucial for advancing AD treatment strategies.