Abstract
Alzheimer’s disease is a severe neurodegenerative disorder that results in loss of memory and cognition (Canter et al. 2016). In order to (1) investigate whether and how gene expression in the molecularly distinct cell types of the human brain is affected in Alzheimer’s disease and (2) to map the cellular diversity of the aged human brain at single-cell resolution on a genome-wide scale, we analyzed human post-mortem brain tissue of 12 AD patients and 12 aged-matched normal individuals using single-nucleus RNA-sequencing. A total of 3264 adult human postmortem prefrontal cortex nuclei were sequenced. We identified six distinct cell types and two pathology associated cell clusters in the human postmortem prefrontal cortex tissue. Finally, data analysis revealed dramatic differences in gene expression in both neurons and oligodendrocytes of individuals carrying one or more copies of the APOE4 allele compared to subjects that do not carry an APOE4 allele.