Rare (MAF <1%), but large-impact hypomorphic variants in TREM2 significantly increase AD risk4-7 and related conditions.8-12 Rare recessive TREM2 mutations can also cause Nasu-Hakola disease characterized by fragility fractures, brain white matter changes and dementia in early adulthood.13 The gene discussed is TREM2; the disease is Nasu-Hakola disease.