In the search for a deeper understanding of Alzheimer’s disease (AD), scientists are turning their attention to long non-coding RNAs (lncRNAs)—a type of RNA that doesn’t produce proteins but plays a crucial role in regulating gene activity. A recent study led by researchers from the University of Lübeck has taken a major step forward by conducting the largest analysis to date of lncRNA expression in human brain samples using RNA sequencing.

The research team analyzed data from 1,220 brain samples across three different brain regions commonly affected in AD: the entorhinal cortex (where AD begins), the dorsolateral prefrontal cortex, and the fusiform gyrus. By comparing samples from individuals with and without Alzheimer’s, they identified 356 lncRNAs that were consistently different between the two groups. Many of these lncRNAs were already known to be involved in AD, but several dozen—including Lnc-TNFRSF13B-2 and GSN-AS1—were completely new to the field.

A schematic presentation illustrating the general workflow of this study. Boxes and arrows with broken lines indicate the sensitivity analyses conducted on different data processing steps. EC: Entorhinal cortex; DLPFC: Dorsolateral prefrontal cortex; FG: Fusiform gyrus

What makes this study so impactful is not just its size, but its focus on the entorhinal cortex, a critical area for memory that’s among the first to show signs of damage in AD. The team’s findings point to biological processes like neuron and synapse development, suggesting that lncRNAs may play an active role in the disease’s progression. These insights open new doors for understanding how Alzheimer’s develops and could pave the way for future research into early detection and treatment strategies.