Rationale and emerging evidence for microglial replacement in Alzheimer's disease.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Microglia, once seen as passive cells, are now known as active regulators of brain homeostasis and synaptic remodeling.
• Microglial interactions with genetic risk factors and aging are central to Alzheimer's disease (AD) pathogenesis.
• Understanding microglial roles is crucial for developing effective AD therapies.

Purpose of the Study:

• To summarize recent advances in understanding microglial contributions to AD.
• To explore how microglia respond to amyloid-beta and tau pathologies.
• To review novel therapeutic strategies targeting microglial function.

Main Methods:

• Genetic and transcriptomic studies to identify microglial roles in AD.
• Analysis of microglial responses to amyloid-beta and tau pathology.
• Review of emerging microglial replacement therapies.

Main Results:

• Microglia adopt diverse functional states in response to AD pathology, with context-dependent protective or detrimental effects.
• Genetic and transcriptomic data highlight microglia's central role in AD pathogenesis.
• Microglial replacement strategies show promise in preclinical AD models.

Conclusions:

• Microglia are key players in Alzheimer's disease, influencing neurodegeneration through dynamic functional states.
• Targeting microglial function, particularly through cell replacement therapies, offers a promising new therapeutic avenue for AD and other neurodegenerative diseases.