Clinical Report: Adjusting Microglial States in Alzheimer’s Disease
Overview
This review discusses the shift in Alzheimer's disease treatment from pathology removal to regulating the brain microenvironment, emphasizing the role of microglia in disease progression.
Background
Alzheimer’s disease (AD) represents a significant public health challenge, particularly as the global population ages. Traditional approaches focusing solely on amyloid-beta have not consistently yielded sustained clinical benefits.
Data Highlights
No numerical data presented in the article.
Key Findings
Anti-Aβ monoclonal antibodies like lecanemab and donanemab show statistically significant disease-modifying effects but limited cognitive improvement.
Microglia are active determinants of AD susceptibility and progression, influenced by genetic and environmental factors.
Microglial states are dynamic and influenced by plaque proximity, disease stage, genotype, age, sex, and tissue context.
Three key drivers of microglial dysfunction include the TREM2–APOE lipid-sensing axis, complement-mediated synaptic elimination, and immunometabolic reprogramming.
Clinical Implications
Clinicians should consider the multifaceted role of microglia in Alzheimer's disease when evaluating treatment options.
Conclusion
The evolving understanding of microglial roles in Alzheimer's disease necessitates a shift in therapeutic strategies.
