Single‐cell transcriptomics analysis identifies oligodendrocyte‐microglia crosstalk modulated by TREM2‐R47H and exacerbated by APOE4 in Alzheimer's disease

In summary, this study suggests possible synergistic effects of APOE4-carrier and TREM2-R47H-carrier status on OPC, oligodendrocyte, and inhibitory neuron abundance and transcriptional profiles. Specifically, OPCs and oligodendrocytes show a strong association with TREM2-R47H that is exacerbated by APOE genotype, a finding that is reflected in the human cohort. Hence, further classification of differences between joint APOE-TREM2 genotypes will improve our understanding of glial cell alterations in AD, and could lead to novel cell type-specific therapeutic interventions for AD and other AD-related dementia if broadly applied.