Uncovering Spatiotemporal and Functional Dynamics of Long Non-coding RNAs During Alzheimer's Progression in the Human...

Increasing prevalence of Alzheimer's disease, driven by population aging, highlights the need to investigate its underlying molecular mechanisms. Within this context, long non-coding RNAs (lncRNAs) have emerged as a key regulatory layer. To advance the understanding of lncRNA dysregulation and function during Alzheimer's disease progression, we reanalyzed publicly available single-nucleus RNA sequencing (snRNA-seq) datasets. The selected transcriptomic datasets were integrated and subjected to differential expression and genomic co-localization correlation analyses to infer putative cis-regulatory mechanisms. Our results reveal conserved cell-type composition and a shared transcriptional trajectory across brain regions during Alzheimer's disease progression. In contrast, lncRNAs displayed marked cell-type and context specificity and formed coordinated expression patterns with neighboring genes within defined chromatin contexts. These associations suggest potential cis-regulatory roles and implicate lncRNAs in processes such as synaptic plasticity and maladaptive oligodendrocyte differentiation linked to myelin dysfunction. While these findings are primarily hypothesis-generating, they provide a cross-regional framework and a prioritized set of candidate lncRNAs for future functional investigation in Alzheimer's disease.