We also found that the TREM2R47H gene variant was associated with changes in cognitive decline in the large cohort of HD patients, whereas 2 of 3 TLR4 single nucleotide polymorphisms assessed were associated with changes in motor progression in this same group.
The stimulation of cGAMP-STING-IRF3 pathway induces expression of triggering receptor expressed on myeloid cells 2 (TREM2), and the overexpression of TREM2 further decreases Aβ deposition and neuron loss while improves AD pathomorphology and cognitive impairment.
This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT) and APPswe/PS1dE9 mice.
Moreover, genome-wide association studies have linked variants in several immune genes, such as TREM2 and CD33, the expression of which in the brain is restricted to microglia, with cognitive dysfunctions in LOAD.
A variant upstream of TREM2, rs7759295(C) , is independently associated with an increased tau tangle density (p = 4.9 × 10(-4) ), an increased burden of neurofibrillary tangles (p = 9.1 × 10(-3) ), and an increased rate of cognitive decline (p = 2.3 × 10(-3) ).