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Microglia in Alzheimer's Disease: Risk Factors and Inflammation
Atsuko Katsumoto1, Hideyuki Takeuchi1, Keita Takahashi1
1Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Abstract:
Microglia are resident immune cells in the central nervous system (CNS) that originate from myeloid progenitor cells in the embryonic yolk sac and are maintained independently of circulating monocytes throughout life. In the healthy state, microglia are highly dynamic and control the environment by rapidly extending and retracting their processes. When the CNS is inflamed, microglia can give rise to macrophages, but the regulatory mechanisms underlying this process have not been fully elucidated. Recent genetic studies have suggested that microglial function is compromised in Alzheimer's disease (AD), and that environmental factors such as diet and brain injury also affect microglial activation. In addition, studies of triggering receptor expressed on myeloid cells 2-deficiency in AD mice revealed heterogeneous microglial reactions at different disease stages, complicating the therapeutic strategy for AD. In this paper, we describe the relationship between genetic and environmental risk factors and the roles of microglia in AD pathogenesis, based on studies performed in human patients and animal models. We also discuss the mechanisms of inflammasomes and neurotransmitters in microglia, which accelerate the development of amyloid-β and tau pathology.
Insights
Microglia, the brain's immune cells, play a complex role in Alzheimer's disease (AD). Understanding their genetic and environmental influences is key to developing effective AD therapies.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are the primary immune cells of the central nervous system (CNS).
- They originate from embryonic yolk sac progenitors and are distinct from circulating monocytes.
- Microglial dynamics are crucial for CNS homeostasis, but their role in neuroinflammation and disease is complex.
Purpose of the Study:
- To elucidate the relationship between genetic and environmental risk factors in Alzheimer's disease (AD) pathogenesis.
- To explore the multifaceted roles of microglia in AD development.
- To discuss the impact of inflammasomes and neurotransmitters on microglial activation and AD pathology.
Main Methods:
- Review of genetic studies in human patients and animal models of AD.
- Analysis of environmental factors (diet, brain injury) influencing microglial activation.
- Examination of microglial heterogeneity and responses in different AD stages.
Main Results:
- Genetic factors compromise microglial function in AD.
- Environmental influences significantly affect microglial activation.
- Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency shows heterogeneous microglial reactions in AD mice.
- Inflammasomes and neurotransmitters in microglia accelerate amyloid-beta and tau pathology.
Conclusions:
- Microglial dysfunction is implicated in AD pathogenesis.
- Therapeutic strategies for AD must consider both genetic and environmental factors affecting microglia.
- Further research into microglial mechanisms, including inflammasomes and neurotransmitters, is crucial for AD treatment.