TREM2 and Alzheimer disease: Clinical observations have shown the involvement of TREM2 in Nasu-Hakola disease (see Role of Microglia in Neurodevelopmental Disease), and recently, TREM2 mutations have been associated with an increased risk of developing amyotrophic lateral sclerosis (Cady et al., 2014), frontotemporal dementia (FTD) (Thelen et al., 2014) and AD (Jonsson et al., 2013).