MS4A4A and Alzheimer disease: This work had several important implications: 1) elucidates the functional mechanism by which MS4A4A affects AD risk, modulation of TREM2 levels; 2) demonstrates that TREM2 involvement in AD pathogenesis is not limited to mutation carriers; 3) pharmaceutical targeting of MS4A4A, TGFBR2 or NECTIN2 are valid therapeutic approaches to modulate TREM2 levels and in consequence, AD risk.