The results of Zhou et al.’s study suggested that lipopolysaccharide (LPS)-induced hyperactive TLR4 might inhibit the negative effect of TREM2 on regulating inflammation, and the imbalance of microglial TLR4/TREM2 might be a potential link between Alzheimer’s disease and systemic inflammation (58). Here, TREM2 is linked to early-onset autosomal dominant Alzheimer disease.