Differential roles of ApoE isoforms in regulation of inflammatory cytokine expression

ApoE Ɛ4 has long been known as a top genetic risk factor in the development of late‐onset Alzheimer’s disease (LOAD). More recently the genetic variants of the innate immune receptor TREM2 such as R47H, which confers a similar risk as ApoE4 in LOAD, have been identified as genetic risk factors in the development of many neurodegenerative diseases with dysregulated neuroinflammation. TREM2 is expressed highly on microglia and macrophages and plays key roles in inflammation regulation. Our previous study (Dorey et al. 2017) has shown that ApoE isoforms play differential roles in Aβ‐induced inflammatory response. Atagi et al (2015) identified that ApoE is a ligand for TREM2. Given the physiological relationship between ApoE and TREM2 while also considering the three isoforms of ApoE, it is crucial to investigate and understand the mechanisms underlying the possibility differential ApoE isoform signaling through TREM2 surface receptor.