Novel insights into the role of TREM2 in cerebrovascular diseases

Abstract

Cerebrovascular diseases (CVDs) include conditions such as stroke, cerebral amyloid angiopathy (CAA) and cerebral small vessel disease (CSVD), which contribute significantly to global morbidity and healthcare burden. The pathophysiology of CVD is complex, involving inflammatory, cellular and vascular mechanisms. Recently, research has focused on triggering receptor expressed on myeloid cells 2 (TREM2), an immune receptor predominantly found on microglia. TREM2 interacts with multiple signalling pathways, particularly toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB), inhibiting patients’ inflammatory response. This receptor plays an essential role in both immune regulation and neuroprotection. TREM2 deficiency or dysfunction is associated with impaired microglial responses, exacerbated neurodegeneration and neuroinflammation. Up until recently, TREM2 related studies have focused on neurodegenerative diseases (NDs), however a shift in focus towards CVDs is beginning to take place. Advancements in CVD research have focused on developing therapeutic strategies targeting TREM2 to enhance recovery and reduce long-term deficits. These include the exploration of TREM2 agonists and combination therapies with other anti-inflammatory agents, which may synergistically reduce neuroinflammation and promote neuroprotection. The modulation of TREM2 activity holds potential for innovative treatment approaches aimed at improving patient outcomes following cerebrovascular insults. This review compiles current research on TREM2, emphasising its molecular mechanisms, therapeutic potential, and advancements in CNS disease research.