Finally, we did not examine the potential role of TREM2 in defining microglial phenotypes, as frequencies of AD-relevant pathogenic mutations are small; these rare mutations have demonstrated relevance to plaque-associated microglial cell phenotypes, and the soluble cleavage product of this myeloid receptor is elevated in the CSF of individuals with untreated HIV disease [53, 57]. This evidence concerns the gene TREM2 and Alzheimer disease.