Automated image segmentation uncovers the role of CD74high human microglia in cognitive decline.

The role of activated microglia in Alzheimer's disease (AD) is well established; the proportion of stage III activated microglia has been associated with AD and cognitive decline, but this morphologically defined subtype is relatively uncommon (1-2% of microglia) and its cellular function is unknown. Single-cell RNA-sequencing revealed CD74 as a marker gene that is enriched in immunologically active microglial subtypes associated with AD. Here, we evaluated the relationship between CD74 expression, AD-related traits, and microglial morphology using dorsolateral prefrontal cortex samples from two brain collections (ROSMAP: n=63, NYBB: n=91).

A proteogenomic tool uncovers protein markers for human microglial states.

Human microglial heterogeneity has been largely described using transcriptomic data. Here, we introduce a microglial proteomic data resource and a Cellular Indexing of Transcriptomes and Epitopes by Sequencing panel enhanced with antibodies targeting 17 microglial cell surface proteins (mCITE-Seq). We evaluated mCITE-Seq on HMC3 microglia-like cells, induced-pluripotent stem cell-derived microglia (iMG), and freshly isolated primary human microglia.