Microglial TREM2 at the Intersection of Brain Aging and Alzheimer’s Disease

Wenhui Qu, Ling Li

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


As resident immune cells of the brain, microglia serve pivotal roles in regulating neuronal function under both physiological and pathological conditions, including aging and the most prevalent neurodegenerative disease, Alzheimer’s disease (AD). Instructed by neurons, microglia regulate synaptic function and guard brain homeostasis throughout life. Dysregulation of microglial function, however, can lead to dire consequences, including aggravated cognitive decline during aging and exacerbated neuropathology in diseases. The triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial function. Loss-of-function variants of TREM2 are associated with an increased risk of AD. TREM2 orchestrates the switch of microglial transcriptome programming that modulates microglial chemotaxis, phagocytosis, and inflammatory responses, as well as microglial regulation of synaptic function in health and disease. Intriguingly, the outcome of microglial/TREM2 function is influenced by age and the context of neuropathology. This review summarizes the rapidly growing research on TREM2 under physiological conditions and in AD, particularly highlighting the impact of TREM2 on neuronal function.

Original languageEnglish (US)
Early online dateSep 2 2021
StatePublished - Sep 2 2021

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by grants from the National Institute on Aging of the National Institutes of Health (AG056976 and AG058081) and the College of Pharmacy at the University of Minnesota.

Publisher Copyright:
© The Author(s) 2021.


  • aging
  • Alzheimer’s disease
  • cognitive function
  • microglia
  • synaptic plasticity
  • TREM2

PubMed: MeSH publication types

  • Journal Article


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