Genetic deficits and loss of function for the triggering receptor expressed in 
myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning 
stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have 
been associated with deficiencies in phagocytosis and the innate immune system 
in Alzheimer's disease. In this study, we provide evidence that TREM2 is 
downregulated in samples of sporadic Alzheimer hippocampal CA1 compared with 
age-matched controls. A nuclear factor-кB (NF-кB)-sensitive miRNA-34a (encoded 
at chr1p36.22), upregulated in Alzheimer's disease, was found to target the 299 
nucleotide human TREM2 mRNA 3'-untranslated region (3'-UTR) and downregulate the 
expression of a TREM2-3'-UTR reporter vector. A stabilized anti-miRNA-34a 
(AM-34a) quenched this pathogenic response. The results suggest that an 
epigenetic mechanism involving an NF-кB-mediated, miRNA-34a-regulated 
downregulation of TREM2 expression may shape innate immune and phagocytic 
responses that contribute to inflammatory neurodegeneration.