‘Jumping genes’ may explain inflammatory trigger of Alzheimer’s disease

SAN ANTONIO, Texas — The pathology of Alzheimer’s disease and other neurodegenerative diseases continue to puzzle scientists. However, UT Health San Antonio scientists have made a novel discovery, finding a possible inflammatory trigger for Alzheimer’s as well as a rare brain disorder called supranuclear palsy.

“We have identified a new trigger of brain inflammation in these disorders,” says study author Elizabeth Ochoa, PhD, from UT Health San Antonio in a university release.

Alzheimer’s disease and progressive supranuclear palsy are characterized by toxic deposits of a protein called tau in the brain. Ochoa and the team’s work shows that tau-induced “jumping genes,” which can move around or copy themselves to other locations, form double-stranded RNA. This developed RNA structure mimics the inflammatory trigger seen in viral infections, allowing researchers to draw connections.

“Transposable elements — the so-called jumping genes — are a new area of interest in understanding Alzheimer’s disease. Our study provides new insights into how they can drive the disease process in addition to their ability to jump,” Ochoa adds. “These double-stranded RNAs look like a virus to the immune system even though the jumping genes are a part of our normal genome.”

To better understand the double-strand RNA, the researchers used animal models to examine brain inflammation in humans.

“To ensure that what we found in our fruit fly experiments is relevant to mammalian disease, we also studied brain tissue from mouse models and from postmortem human brains affected by tauopathy,” Ochoa continues.

The team was able to find and compare these abnormalities in both postmortem brain tissue from those with Alzheimer’s disease and progressive supranuclear palsy, as well as in the brains of fruit fly and mouse models with deformed tau protein structure.

“As we are currently targeting jumping gene activation in a local Phase II clinical trial for patients with Alzheimer’s disease, it’s important to understand the full repertoire of toxic molecules, including double-stranded RNAs, that jumping genes produce,” adds senior study author Bess Frost, PhD.

The researchers believe that these findings open doors to better understanding genomic and metabolic features implicated in neurodegenerative diseases, therefore improving the approach to prevention and care in this patient population. Alzheimer’s affects millions of people around the world, leading to debilitating memory loss and a declining ability to think. There is currently no cure, but more research in this area can help to improve prognosis and tackle preventative measures that improve and maintain quality of life for those who have it or those at risk of developing it.

The findings appear in the journal Science Advances.

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