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Published on: November 9, 2018
A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer's disease
Yongjin Yoo1, Gernot Neumayer1, Yohei Shibuya1
1Institute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
Alzheimer's disease (AD) remains one of the grand challenges facing human society. Much controversy exists around the complex and multifaceted pathogenesis of this prevalent disease. Given strong human genetic evidence, there is little doubt, however, that microglia play an important role in preventing degeneration of neurons. For example, loss of function of the microglial gene Trem2 renders microglia dysfunctional and causes an early-onset neurodegenerative syndrome, and Trem2 variants are among the strongest genetic risk factors for AD. Thus, restoring microglial function represents a rational therapeutic approach. Here, we show that systemic hematopoietic cell transplantation followed by enhancement of microglia replacement restores microglial function in a Trem2 mutant mouse model of AD.
Insights
Restoring microglial function via cell transplantation can reverse neurodegeneration in a mouse model of Alzheimer's disease (AD). This approach offers a promising therapeutic strategy for AD by enhancing the protective roles of microglia.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Alzheimer's disease (AD) pathogenesis is complex, but microglia are known to protect neurons.
- The microglial gene Trem2 is crucial; its loss causes neurodegeneration, and variants are major AD risk factors.
Purpose of the Study:
- To investigate if restoring microglial function can be a therapeutic strategy for Alzheimer's disease.
- To evaluate the efficacy of hematopoietic cell transplantation in enhancing microglial replacement and function in a Trem2 mutant AD mouse model.
Main Methods:
- Systemic hematopoietic cell transplantation was performed in Trem2 mutant mice.
- Microglia replacement and function were assessed post-transplantation.
Main Results:
- Hematopoietic cell transplantation successfully restored microglial function in the Trem2 mutant AD mouse model.
- Enhanced microglia replacement was observed, indicating successful restoration of microglial activity.
Conclusions:
- Restoring microglial function through cell transplantation is a viable therapeutic approach for Alzheimer's disease.
- This study highlights the potential of targeting microglia for AD treatment, particularly in cases involving Trem2 mutations.
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