June 30, 2026
Cleveland.com article authored by Julie Washington and advance local express, published on June 30, 2026
CLEVELAND, Ohio — A shortage of nitric oxide—a gas the body produces naturally—may be tied to faster disease progression in Alzheimer’s patients, according to researchers at University Hospitals and Case Western Reserve University.
The findings, published recently in the journal Molecular Cell, center on a process called alternative splicing. In this process, a single gene can produce multiple sets of instructions. Nitric oxide plays a key role in controlling how genes are edited in the brain, researchers said.
When nitric oxide levels drop, gene editing activity slows, the study suggests. In Alzheimer’s patients, that slowdown tracks with more plaque buildup and faster memory loss.
“We showed that nitric oxide levels are decreased in the brains of patients with Alzheimer’s disease, and that this loss of control over gene splicing correlates with worse clinical outcomes,” said lead author Dr. Jonathan Stamler, president and co-founder of Harrington Discovery Institute at UH.
“In other words, lower nitric oxide levels lead to reduced gene-splicing activity, which is associated with increased plaque buildup and more rapid memory loss,” Stamler said.
The study also challenges a long-standing assumption that high nitric oxide levels contributed to Alzheimer’s disease.
“This new discovery changes that paradigm,” he said.
The team also identified specific enzymes that strip nitric oxide from brain proteins involved in splicing, rendering those proteins unable to function properly. Blocking those enzymes could be a way to restore nitric oxide levels and potentially slow the disease, researchers said.
Alzheimer’s disease is a top 10 leading cause of death in the United States, according to the Centers for Disease Control and Prevention. The number of people living with Alzheimer’s is projected to double from 6.9 million in 2020 to nearly 14 million people by 2060, according to federal data.
Cardiology
University Hospitals - Cleveland
Harrington Investigators