Tracking microRNA clues in vascular dementia
New data-driven research may hold the keys to therapeutic targets in the future.
An ambitious search for brain microRNA biomarkers or therapeutic targets for cerebrovascularrelated cognitive decline is the focus of new research and a robust discussion at “Unraveling the Molecular Underpinnings of Brain Injury After Ischemia and Hemorrhage.”
The novel and complex research findings in mouse models are just one of the approximately 130 biomarkers Tracy D. Farr, PhD, and her team discovered. Farr, an associate professor at the University of Edinburgh in the U.K., is among the presenters at Thursday’s session. Her presentation, “A Role for miRNAs in Cerebrovascular Disease,” pulls the curtain back on how chronic cerebrovascular disease can lead to dementia.
“Ischemic stroke hemorrhage and even some form of dementia are consequences of cerebrovascular disease,” Farr said. “What was unique about our approach is that we had no idea what we were looking for. We harvested microRNAs from animal models and used a data-driven approach to tell us what we should be looking for in hypoperfused brains. We are currently exploring some promising microRNAs to see what brain cell types they are present in. We have confirmed one of our most promising targets also increases when human cells have been deprived of oxygen. It gives us hope that if we see it in the mouse, we’re seeing it in the human as well.”
Conditions such as longstanding hypertension and hypoperfusion can progressively damage blood vessels, stiffening arteries, triggering inflammation and ultimately encouraging dysfunction. This is associated with memory and cognitive impairments.
“Many people think of dementia as Alzheimer’s disease. But vascular contributors are significant and sometimes overlooked,” Farr said. “Now, we have this data we will make it open access, giving others an opportunity to advance their own research.”
Unlike traditional imaging biomarkers, microRNAs offer a mechanistic view of pathology, Farr said. Her team’s research to examine tiny, 20 nucleotide RNAs that help regulate gene expression through epigenetic mechanisms is a common approach in cancer, she said. Yet, the impact in cerebrovascular disease–related cognitive decline has remained relatively unexplored.
“In total, across three different brain regions, we identified about 130 region specific microRNAs that changed,” Farr said. “Now the hard part is characterizing them.”
One of the most valuable outcomes of the project may be the dataset itself. Once published, it will become fully open access, enabling researchers worldwide to explore microRNAs tied to cerebrovascular disease — and potentially accelerate discoveries far beyond Farr’s own lab.
“If someone sees a microRNA they’re already interested in, this dataset might show it’s important in cerebrovascular disease, too,” she noted.
In looking ahead to clinical translation, Farr cautioned that clinical applications are still distant. Her next grant aims to continue to look at some of the top candidates and to study human brain tissue from patients with vascular dementia to confirm that the same microRNA changes appear in real-world disease.
“It could take a long time before this is directly translatable,” she said. “But it’s promising, and it requires more investigation to understand the mechanisms and confirm these targets matter.”
With the identification of so many potential molecular clues, the field may be on the cusp of a new era — one where vascular dementia can be detected, understood more deeply and one day perhaps even treated through pathways hidden within the smallest regulators of gene expression, Farr said.
