# Cellular insights into transposable elements in Alzheimer’s disease

## TL;DR

This study explores how transposable elements contribute to Alzheimer's disease by analyzing their expression in different brain cell types.

## Contribution

The study identifies cell-type-specific transposable element activation in Alzheimer’s disease using single-nucleus RNA sequencing and chromatin accessibility data.

## Key findings

- 508 differentially expressed transposable element loci were identified, with 84.3% upregulated in Alzheimer’s disease.
- Transposable element dysregulation was most prominent in excitatory neurons and oligodendrocytes, dominated by SINE and LINE elements.
- Several dysregulated transposable elements overlapped regulatory regions near key Alzheimer’s disease-associated genes.

## Abstract

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.

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.

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.

These findings highlight cell-type-specific TE activation in AD and provide a foundation for investigating TE-mediated regulatory disruption and its therapeutic potential.