McEntee Cali M, LaRocca Thomas J
Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
Center for Healthy Aging, Colorado State University, Fort Collins, CO, USA.
Mol Neurobiol. 2025 Jun 19. doi: 10.1007/s12035-025-05140-9.
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.
越来越多的证据表明，转座元件（TE）的转录本与阿尔茨海默病（AD）的发病机制有关。然而，尽管最近有对AD进行的单细胞/单细胞核RNA测序（sc/snRNA-seq）研究，但尚未报道TE转录本中的细胞类型特异性模式。因此，我们基于AD患者的前额叶皮质样本，在snRNA-seq数据集中检查了TE转录本。我们分析了143,951个细胞中的基因/TE表达，发现：（1）在大多数脑细胞类型中，TE转录本随AD广泛增加；（2）逆转录转座子转录本在兴奋性神经元中随AD病理变化增加最多；（3）TE基因座在AD中更易转录，尤其是在神经元/兴奋性神经元中。我们还在对AD的批量RNA-seq数据的补充分析中证实了我们的发现。总之，我们的数据为AD大脑中不同细胞类型的TE转录本动态提供了新的见解。
