TREM2 and Nasu-Hakola disease: FTD-like and NHD mutations in TREM2 are described as loss-of-function mutations, as they result in reduced cell surface expression and ligand binding (Kleinberger et al., 2014, Kober et al., 2016, Park et al., 2015), while AD-associated variants are thought to reduce the affinity of TREM2 for its ligands (Kober et al., 2016, Yeh et al., 2016).