A brain atlas of astrocyte transcriptomics unveils complex states and responses to Alzheimer’s disease neuropathology

Amyloid‐β plaques and neurofibrillary tangles in the Alzheimer’s disease (AD) brain are accompanied by prominent morphological and functional changes in astrocytes, collectively termed reactive astrogliosis. Single‐nuclei RNA‐sequencing (snRNA‐seq) has begun to unveil the molecular underpinnings of AD reactive astrocytes but technical challenges, including low numbers of nuclei and/or sequencing depth, and the lack of comparisons across brain regions have limited the full picture. Here we present the largest snRNA‐seq study of astrocytes to date across five brain regions.