Perturbation of the transcriptome: implications of the innate immune system in Alzheimer's disease

•Immune gene dysregulation in AD brains is linked to Aβ and tau pathology.•Immune gene dysregulation is consistently observed in AD blood as well.•Studies on isolated brain cells can provide clearer picture on immune dysregulation.•TREM2 is a unique gene with firm support from genetic and transcriptomic studies.

Alzheimer's disease (AD) is a neurodegenerative disease with broad impact. Although Aβ and tau have been proposed as the key molecules in the disease mechanism, comprehensive understanding of AD pathogenesis requires a systemic view at the genomic level. From studies on the brain transcriptome of AD, we have gradually realized the contribution of the immune system to AD development. Recent explorations on the blood transcriptome of AD patients have revealed robust immune activation in the peripheral blood. The combination of transcriptome studies and other types of studies has further elucidated the roles of specific immune pathways in distinct cell types during AD development and highlighted the critical contributions from immune genes such as TREM2.