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Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Rationale and emerging evidence for microglial replacement in Alzheimer's disease
1Department of Neuroscience, Korea University College of Medicine, Seoul, Republic of Korea; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Abstract:
Microglial biology in Alzheimer's disease (AD) has become a major focus of investigation, aiming to define how these cells contribute to neurodegeneration and to develop new therapeutic strategies. Once regarded as passive responders, microglia are now recognized as active regulators of brain homeostasis, immune signaling, and synaptic remodeling. Their interactions with genetic risk variants and age-related changes are increasingly understood to play central roles in AD pathogenesis. In this mini-review, we summarize recent progress in identifying microglial contributions to AD through genetic and transcriptomic studies. We discuss how microglia respond to amyloid-β and tau pathology by shifting into diverse functional disease-associated states, which may either protect or harm the brain depending on context and disease stage. We also outline the rationale for targeting microglia through replacement strategies and review emerging approaches using circulation-derived myeloid cells (CDMCs), and human pluripotent stem cell-derived microglia-like cells. These replacement methods have shown potential to rectify microglial functions and modify AD-related pathology in preclinical models, offering a novel therapeutic direction for neurodegenerative diseases.
Insights
Microglia actively regulate brain health in Alzheimer's disease (AD). New research explores targeting these cells, including stem cell-derived microglia, as a potential therapeutic strategy for AD.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia, once seen as passive cells, are now known as active regulators of brain homeostasis and synaptic remodeling.
- Microglial interactions with genetic risk factors and aging are central to Alzheimer's disease (AD) pathogenesis.
- Understanding microglial roles is crucial for developing effective AD therapies.
Purpose of the Study:
- To summarize recent advances in understanding microglial contributions to AD.
- To explore how microglia respond to amyloid-beta and tau pathologies.
- To review novel therapeutic strategies targeting microglial function.
Main Methods:
- Genetic and transcriptomic studies to identify microglial roles in AD.
- Analysis of microglial responses to amyloid-beta and tau pathology.
- Review of emerging microglial replacement therapies.
Main Results:
- Microglia adopt diverse functional states in response to AD pathology, with context-dependent protective or detrimental effects.
- Genetic and transcriptomic data highlight microglia's central role in AD pathogenesis.
- Microglial replacement strategies show promise in preclinical AD models.
Conclusions:
- Microglia are key players in Alzheimer's disease, influencing neurodegeneration through dynamic functional states.
- Targeting microglial function, particularly through cell replacement therapies, offers a promising new therapeutic avenue for AD and other neurodegenerative diseases.
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