Here, generating single-nucleus RNA and ATAC-seq data from individuals of various backgrounds, we show that specific signatures in multiple cell classes – GPNMB+ microglia, SERPINH1+ astrocytes, a subset of CUX2+/RORB+ glutamatergic neurons, and a range of oligodendrocytic factors – show similar associations with AD pathology and cognitive phentoypes in African-American, Non-Latin White, Latin individuals. Here, SERPINH1 is linked to Alzheimer disease.