Inflammation has triggered new clues to Alzheimer's disease

Scientists at the University of Texas San Antonio Health Sciences Center (UT Health SAN ANTONIO) reported today that inflammatory triggers present during viral infections are elevated
in Alzheimer's disease and progressive supranuclear palsy, a rare brain disease.

Study author Elizabeth Ochoa of the University of Texas Health Center in San Antonio said: "We have identified new triggers of brain inflammation in these diseases
.
" For this reason, she said, the discovery, published in Science Advances
, is novel.

Alzheimer's disease and progressive supranuclear palsy are characterized by toxic deposits of a protein called tau
.
Their research found that tau-induced "jumping genes" — which can relocate or replicate themselves to other locations in the genome — form double-stranded RNA
.
This abnormal RNA mimics the inflammatory triggers
that are also present in viral infections.

"Transposable factors — so-called jumping genes — are a new area
of interest in understanding Alzheimer's disease.
Our research provides new insights
into how they can drive disease progression beyond their ability to jump.
To the immune system, these double-stranded RNAs look like viruses, even though jumping genes are part of
our normal genome.
”

The researchers detected the accumulation
of double-stranded RNA in postmortem brain tissue in patients with Alzheimer's disease and progressive supranuclear palsy, as well as in the brains of mouse and tau disease fruit fly models.

"We found a large number of deposits of double-stranded RNA in astrocytes that provide metabolic support to neurons, regulate neurotransmitters, and maintain the integrity
of the blood-brain barrier.
" "In aging and disease, astrocytes respond to
damage and disruption of the neuronal environment.
Our findings open new doors
to understanding astrocyte biology and its role in transposable factor control.
”

In Alzheimer's and other neurodegenerative diseases, the loss of neurons (cells of the central nervous system) is gradual
.

The researchers conducted experiments on fruit flies to quickly test their questions
about double-stranded RNA and inflammation in the brain.
"To make sure that what we found in fruit fly experiments is related to mammalian disease, we also looked at mouse models and brain tissue
from postmortem human brains affected by mizoaur disease," Ochoa said.

"Since we are currently targeting jumping gene activation in local phase II clinical trials for Alzheimer's disease patients, it is important
to understand the full arsenal of toxic molecules, including double-stranded RNA, produced by jumping genes.
"

essay