Single-Cell Transcriptome Patterns of Transposable Elements in Alzheimer's Disease.

Growing evidence implicates transcripts from transposable elements (TEs) in the pathogenesis of Alzheimer's disease (AD). However, despite recent single-cell/nucleus RNA sequencing (sc/snRNA-seq) studies of AD, cell type-specific patterns in TE transcripts have not been reported. Therefore, we examined TE transcripts in snRNA-seq datasets based on prefrontal cortex samples from AD patients. We analyzed gene/TE expression in 143,951 cells and found that: (1) TE transcripts are broadly increased with AD in most brain cell types; (2) retrotransposon transcripts are most increased with AD pathology in excitatory neurons; and (3) TE loci are more transcriptionally accessible in AD, especially in neurons/excitatory neurons. We also confirmed our findings in complementary analyses of bulk RNA-seq data on AD. Together, our data provide novel insight into TE transcript dynamics across different cell types in the AD brain.