Single nucleus RNA-seq profiling of WT and 5xFAD AD mouse models, across ages.

Supplementary information for manuscript, Titled: Unique disease-associated astrocytes in Alzheimer’s disease

Abstract

The role of non-neuronal cells in Alzheimer’s disease (AD) is largely unknown. Here, single nucleus RNA-seq shows changes in the composition and state of multiple cell types in the 5xFAD mouse model of AD. In particular, we identified a unique population of disease-associated astrocytes (DAAs) in AD. Computational inference predicted that DAAs are derived from a homeostatic Gfap-low astrocyte population. DAAs appeared at early disease stages and increased in abundance with age. Similar cells were found in aged WT mice and human brains, suggesting they are linked to both genetic and age-related factors. Our results highlight an important role for astrocytes in the cellular cascade associated with AD progression, and may provide a novel target for therapeutic intervention.