Dissecting the Cellular Landscape of the Alzheimer’s Brain: Disease Associated Astrocytes

Alzheimer’s disease (AD) is one of the most pressing global medical issues to date with no effective therapeutic strategies. Much remains unknown regarding the role of non-neuronal cells and the crosstalk between them in Alzheimer’s disease (AD). We used single nucleus RNA-seq to follow changes in cell compositions and expression programs in mouse model of AD and in post mortem human brains. We found changes in the composition and state of multiple cell types in disease. In particular, we found a population of disease-associated astrocytes (DAAs) unique to the AD brain in mice, which appeared at early stages of disease and increased in abundance with age. Computational inference predicted that DAAs are derived from the homeostatic astrocyte population. Similar cells were found in healthy aged WT mice and in aging human brains, suggesting that DAAs are linked to both genetic and age-related factors. Our results highlight an important role for astrocytes in the cellular cascade accompanying AD progression, and may provide a novel target for therapeutic intervention.