TREM2, microglia, and Alzheimer's disease
Qi Qin1, Zhaoqian Teng2, Changmei Liu2
1Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.
Abstract:
Triggering receptor expressed on myeloid cells 2 (TREM2) has been suggested to play a crucial role in Alzheimer's disease (AD) pathogenesis, as revealed by genome-wide association studies (GWAS). Since then, rapidly increasing literature related to TREM2 has focused on elucidating its role in AD pathology. In this review, we summarize our understanding of TREM2 biology, explore TREM2 functions in microglia, address the multiple mechanisms of TREM2 in AD, and raise key questions for further investigations to elucidate the detailed roles and molecular mechanisms of TREM2 in microglial responses. A major breakthrough in our understanding of TREM2 is based on our hypothesis suggesting that TREM2 may act as a multifaceted player in microglial functions in AD brain homeostasis. We conclude that TREM2 can not only influence microglial functions in amyloid and tau pathologies but also participate in inflammatory responses and metabolism, acting alone or with other molecules, such as apolipoprotein E (APOE). This review provides novel insight into the broad role of TREM2 in microglial function in AD and enables us to develop new strategies aimed at the immune system to treat AD pathogenesis.
Insights
Triggering receptor expressed on myeloid cells 2 (TREM2) is vital for microglial function in Alzheimer's disease (AD). This review explores TREM2's multifaceted roles in AD pathology, inflammation, and metabolism, offering new therapeutic strategies.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Genome-wide association studies (GWAS) link Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) to Alzheimer's disease (AD) pathogenesis.
- Increasing research focuses on TREM2's specific roles in AD pathology.
Purpose of the Study:
- To review TREM2 biology and its functions in microglia within the context of AD.
- To elucidate the multiple mechanisms of TREM2 in AD pathogenesis.
- To identify key questions for future research on TREM2's role in microglial responses.
Main Methods:
- Literature review and synthesis of current research on TREM2.
- Analysis of TREM2's involvement in microglial functions.
- Exploration of TREM2's interactions with AD pathologies and other molecules like APOE.
Main Results:
- TREM2 is hypothesized to be a multifaceted regulator of microglial functions essential for AD brain homeostasis.
- TREM2 influences microglial roles in amyloid and tau pathologies.
- TREM2 modulates inflammatory responses and cellular metabolism in AD, potentially interacting with APOE.
Conclusions:
- TREM2 plays a broad and critical role in microglial function relevant to Alzheimer's disease.
- Understanding TREM2's mechanisms offers potential for novel immunomodulatory therapeutic strategies for AD.
- TREM2's involvement spans amyloid/tau pathologies, inflammation, and metabolism, highlighting its complex role.
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