Cellular insights into transposable elements in Alzheimer’s disease

Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide. While advances in single-cell technologies have elucidated cellular diversity and transcriptional changes in AD, the contribution of transposable elements (TEs) to disease pathogenesis remains poorly understood. Methods We integrated published single-nucleus RNA sequencing data from 11 AD patients and 7 controls with chromatin accessibility profiles from ATAC-seq to map the cell type—specific landscape of TE expression and regulation. Results We identified 508 differentially expressed TE loci, 84.3% of which were upregulated in AD, indicating widespread TE activation. TE dysregulation was most prominent in excitatory neurons (319 loci) and oligodendrocytes (165 loci), dominated by SINE (62.8%) and LINE (26.4%) elements. Several dysregulated TEs overlapped regulatory regions near key AD-associated genes including DOC2A , ABCA7 , PTK2B , IL34 , ABCB9 , PLD3 , and TARDBP . Discussion These findings highlight cell-type-specific TE activation in AD and provide a foundation for investigating TE-mediated regulatory disruption and its therapeutic potential.