TREM2 and Cognitive impairment: In this process, TREM2 deficiency disrupts microglial bioenergetics and impairs energy metabolism in the entire mitochondrial metabolism of hippocampal tissue, leading to deep transcriptional rearrangements in hippocampal neurons [59], which also explains why the effects of TREM2 deficiency on the A53T mice first manifest as aggravated cognitive impairment.