Scientists from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered that an inflammatory trigger is elevated in Alzheimer’s disease and progressive supranuclear palsy, a rare brain disorder. The trigger is like an inflammatory factor found with viral infections.
“We have identified a new trigger of brain inflammation in these disorders,” says Elizabeth Ochoa, PhD, an investigator of longevity, aging, Alzheimer’s, and neurodegenerative diseases from UT Health San Antonio.
Both Alzheimer’s disease and progressive supranuclear palsy have toxic deposits of a protein called tau. The proteins induce changes in genes which then relocate, or cause relocation of copies of their own genes, to form double-stranded RNA. This aberrant RNA mimics an inflammatory trigger present in viral infections. They refer to the genes in the relocation process as “jumping genes.”
“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 said, in a statement. “These double stranded RNAs look like a virus to the immune system even though the jumping genes are a part of our normal genome.”
The researchers discovered accumulation of double-stranded RNA in brain tissue (obtained postmortem) from patients with Alzheimer’s disease and progressive supranuclear palsy.
“We found substantial deposits of double-stranded RNA in astrocytes, which are cells that provide metabolic support for neurons, regulate neurotransmitters and maintain blood-brain barrier integrity,” said Bess Frost, PhD, the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders. “In aging and disease, astrocytes respond to injury and disruption of the neuronal environment. Our findings open new doors for understanding astrocyte biology and their role in transposable element control.”
The researchers used fruit flies to examine the properties of the double-stranded RNA and inflammation in the brain. “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 said.
“We are currently targeting jumping gene activation in a 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,” Frost said.
This work is published in Science Advances.