Alzheimer's Disease Research Using Human Microglia
Lih-Fen Lue1,2, Thomas G Beach3, Douglas G Walker4,5
1Banner Sun Health Research Institute, Sun City, AZ, 85351, USA. lih-fen.lue@bannerhealth.com.
Abstract:
Experimental studies of neuroinflammation in Alzheimer's disease (AD) have mostly investigated microglia, the brain-resident macrophages. This review focused on human microglia obtained at rapid autopsies. Studies employing methods to isolate and culture human brain microglia in high purity for experimental studies were discussed. These methods were employed to isolate human microglia for investigation of a number of features of neuroinflammation, including activation phenotypes, neurotoxicity, responses to abnormal aggregated proteins such as amyloid beta, phagocytosis, and the effects of aging and disease on microglia cellular properties. In recent years, interest in human microglia and neuroinflammation has been renewed due to the identification of inflammation-related AD genetic risk factors, in particular the triggering receptor expressed on myeloid cells (TREM)-2. Because of the difficulties in developing effective treatments for AD, there has been a general need for greater understanding of the functions of microglia in normal and AD brains. While most experimental studies on neuroinflammation have employed rodent microglia, this review considered the role of human microglia in experimental studies. This review focused on the development of in vitro methodology for the culture of postmortem human microglia and the key findings obtained from experimental studies with these cells.
Insights
This review highlights the importance of studying human microglia for understanding Alzheimer's disease (AD) neuroinflammation. It details methods for culturing human microglia to investigate their role in AD pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation is a key factor in Alzheimer's disease (AD) pathogenesis.
- Microglia, the brain's resident immune cells, are central to neuroinflammation.
- Most research uses rodent microglia, limiting direct translation to human AD.
Purpose of the Study:
- To review methods for isolating and culturing human microglia from postmortem brain tissue.
- To discuss experimental findings on human microglia in the context of AD.
- To emphasize the significance of human microglia in AD research.
Main Methods:
- Focus on in vitro methodologies for isolating and culturing human microglia.
- Utilizing high-purity human microglia cultures for experimental investigation.
- Review of studies employing these methods to study microglial functions.
Main Results:
- Human microglia exhibit distinct activation phenotypes and neurotoxic properties.
- Microglial responses to amyloid beta and other AD-related proteins were characterized.
- Aging and disease processes significantly alter human microglia cellular properties.
- The role of TREM2 (triggering receptor expressed on myeloid cells 2) in AD pathogenesis was highlighted.
Conclusions:
- In vitro culture of human microglia is crucial for understanding AD.
- Human microglia play a critical role in AD neuroinflammation and disease progression.
- Further research on human microglia is essential for developing effective AD treatments.
