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Multiscale Approximations to Understand the Complex Role of Microglia in Alzheimer's Disease
Patricia Martínez-Tazo1, Marina Mejias-Ortega2,3, Verónica López-López1
1Instituto de Neurociencias CSIC-UMH, Sant Joan, d'Alacant, Spain.
Abstract:
Microglia, the resident innate immune cells of the central nervous system, play a pivotal role in the pathogenesis of Alzheimer's disease (AD). Microglia are now recognized as a highly dynamic and heterogeneous population whose molecular and functional states vary with spatial context, disease stage, and genetic background. Recent discoveries across multiple scales from genetics, molecular and cellular biology, to systems-level imaging and epidemiology have underscored the complex and context-dependent contributions of microglia to the AD cascade. Together, these findings highlight the need for integrative, multiscale approaches that bridge molecular, cellular, and systemic perspectives to elucidate the diverse roles of microglia and their impact on disease progression. This mini-review discusses recent advances in understanding microglial biology across these dimensions and outlines current challenges toward achieving a more unified and therapeutically oriented framework for studying microglia in AD.
Insights
Microglia, the brain's immune cells, are crucial in Alzheimer's disease (AD) pathogenesis. Understanding their complex, context-dependent roles requires multiscale approaches for therapeutic insights.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neurodegenerative Diseases
Background:
- Microglia are key players in Alzheimer's disease (AD) pathogenesis.
- Microglial states are dynamic and heterogeneous, influenced by context, disease stage, and genetics.
Purpose of the Study:
- To review recent advances in understanding microglial biology in AD across multiple scales.
- To identify challenges and propose a unified framework for studying microglia in AD.
Main Methods:
- Integration of findings from genetics, molecular biology, cellular biology, imaging, and epidemiology.
- Multiscale analysis bridging molecular, cellular, and systemic perspectives.
Main Results:
- Recent discoveries reveal complex, context-dependent microglial contributions to the AD cascade.
- Microglial roles vary significantly with spatial context, disease stage, and genetic background.
Conclusions:
- A unified, multiscale approach is essential for elucidating microglial functions in AD.
- Addressing current challenges is critical for developing effective AD therapeutics targeting microglia.
