TREM2 and Alzheimer disease: Heterozygous variants including R47H and R62H are risk factors for Alzheimer's disease (AD), while homozygous loss-of-function in TREM2 causes Nasu-Hakola disease, a severe, early-onset demyelinating dementia presenting as a frontotemporal dementia (FTD) syndrome with cystic bone lesions (2–13).