CD33 and Alzheimer disease: Interestingly, homozygous mutations in TREM2, another microglial cell surface receptor, cause an early onset dementia, Nasu-Hakola disease.17 Heterozygous variants in TREM2 are also a significant risk factor for Alzheimer's disease (AD),18 and genome-wide association studies have linked variants in the microglial receptors CD33 and IRF8 with AD and multiple sclerosis, respectively.19, 20 These findings clearly point to the importance of microglia in the health of the CNS and the need to further study how microglial dysfunction leads to neuronal death.