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TREM2 in Alzheimer's Disease: Microglial Survival and Energy Metabolism
Honghua Zheng1,2, Baoying Cheng1, Yanfang Li1,2
1Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, China.
Abstract:
Alzheimer's disease (AD) is the leading cause of age-related dementia among the elderly population. Recent genetic studies have identified rare variants of the gene encoding the triggering receptor expressed on myeloid cells-2 (TREM2) as significant genetic risk factors in late-onset AD (LOAD). TREM2 is specifically expressed in brain microglia and modulates microglial functions in response to key AD pathologies such as amyloid-β (Aβ) plaques and tau tangles. In this review article, we discuss recent research progress in our understanding on the role of TREM2 in microglia and its relevance to AD pathologies. In addition, we discuss evidence describing new TREM2 ligands and the role of TREM2 signaling in microglial survival and energy metabolism. A comprehensive understanding of TREM2 function in the pathogenesis of AD offers a unique opportunity to explore the potential of this microglial receptor as an alternative target in AD therapy.
Insights
Triggering receptor expressed on myeloid cells-2 (TREM2) variants are key genetic risk factors for Alzheimer's disease (AD). TREM2 influences microglial function, survival, and metabolism, offering potential therapeutic targets for AD.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Alzheimer's disease (AD) is a leading cause of dementia in the elderly.
- Rare variants in the TREM2 gene are significant risk factors for late-onset AD (LOAD).
- TREM2 is crucial for microglial function in response to AD pathologies like amyloid-β plaques and tau tangles.
Purpose of the Study:
- To review recent research on the role of TREM2 in microglia and its relevance to AD pathogenesis.
- To discuss novel TREM2 ligands and their signaling pathways.
- To explore TREM2's role in microglial survival and energy metabolism.
Main Methods:
- Literature review of genetic studies, molecular biology research, and neuropathological findings.
- Analysis of TREM2 expression and function in microglia.
- Investigation of TREM2 signaling pathways and their impact on AD.
Main Results:
- TREM2 variants significantly increase LOAD risk.
- TREM2 modulates microglial responses to amyloid-β and tau.
- New TREM2 ligands and their roles in microglial function are emerging.
- TREM2 signaling impacts microglial survival and metabolic processes.
Conclusions:
- TREM2 plays a critical role in microglial function and AD pathogenesis.
- Understanding TREM2 signaling pathways provides insights into AD mechanisms.
- TREM2 represents a promising therapeutic target for Alzheimer's disease.