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Microglia in Aging and Alzheimer's Disease: A Comparative Species Review
Melissa K Edler1, Isha Mhatre-Winters2,3, Jason R Richardson3
1Department of Anthropology, School of Biomedical Sciences, Brain Health Research Institute, Kent State University, Kent, OH 44240, USA.
Abstract:
Microglia are the primary immune cells of the central nervous system that help nourish and support neurons, clear debris, and respond to foreign stimuli. Greatly impacted by their environment, microglia go through rapid changes in cell shape, gene expression, and functional behavior during states of infection, trauma, and neurodegeneration. Aging also has a profound effect on microglia, leading to chronic inflammation and an increase in the brain's susceptibility to neurodegenerative processes that occur in Alzheimer's disease. Despite the scientific community's growing knowledge in the field of neuroinflammation, the overall success rate of drug treatment for age-related and neurodegenerative diseases remains incredibly low. Potential reasons for the lack of translation from animal models to the clinic include the use of a single species model, an assumption of similarity in humans, and ignoring contradictory data or information from other species. To aid in the selection of validated and predictive animal models and to bridge the translational gap, this review evaluates similarities and differences among species in microglial activation and density, morphology and phenotype, cytokine expression, phagocytosis, and production of oxidative species in aging and Alzheimer's disease.
Insights
Microglia, the brain's immune cells, change with age and Alzheimer's disease. This review compares species to improve animal models for neurodegenerative disease drug development.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Microglia are central nervous system immune cells crucial for neuronal support and response to stimuli.
- Aging profoundly impacts microglia, causing chronic inflammation and increasing susceptibility to neurodegenerative diseases like Alzheimer's.
- Low success rates in translating neurodegenerative disease treatments from animal models to clinics highlight a significant translational gap.
Purpose of the Study:
- To evaluate species-specific similarities and differences in microglial characteristics.
- To aid in selecting validated and predictive animal models for aging and Alzheimer's disease research.
- To bridge the translational gap in neuroinflammation drug development.
Main Methods:
- Comparative review of microglial activation and density across species.
- Analysis of species differences in microglial morphology and phenotype.
- Evaluation of interspecies variations in cytokine expression, phagocytosis, and oxidative species production.
Main Results:
- Identified key similarities and differences in microglial responses to aging and Alzheimer's disease across species.
- Highlighted the importance of considering species-specific data to avoid assumptions of human similarity.
- Provided a framework for understanding how different animal models reflect human microglial behavior.
Conclusions:
- Species-specific differences in microglia are critical for understanding neuroinflammation and neurodegenerative diseases.
- Selecting appropriate animal models based on comparative microglial data is essential for successful drug development.
- Addressing the translational gap requires a nuanced approach that accounts for interspecies variations in microglial function.
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