Nitric Oxide Speeds Alzheimer's in Mice

Half of the mice were further altered to lack iNOS, one of the enzymes that produce nitric oxide, while the other half retained usual iNOS expression. While both groups early developed brain lesions suggestive of Alzheimer's, the mice without the iNOS had a much slower disease progression.

"Stopping iNOS wouldn't cure Alzheimer's, because iNOS expression is not the cause of the disease, but inhibiting the enzyme might slow disease progression considerably—much more effectively than any agents we have now,” said Dr. Flint Beal, chairman of the department of neurology and neuroscience at Weill Cornell.

iNOS has no place in the brain, according to the researchers, but high levels of the enzyme have long been noticed in the brains of Alzheimer's patients. Scientists suspect that an abnormal form of amylolid-beta may serve as an irritant, "fooling” the body into thinking that an infection-like process is underway and spurring iNOS to begin producing nitric oxide. The team's findings were reported in the November 7, 2005, issue of The Journal of Experimental Medicine.

"The findings are preliminary, but drug companies have already developed agents that may safely inhibit the disease-associated form of the enzyme responsible for producing nitric oxide in the human brain,” noted lead research Dr. Carl Nathan, R.A., professor and chairman of the department of microbiology and immunology at Weill Cornell.

The "i” in iNOS (named by Dr. Nathan after its discovery in 1992) stands for "inducible.” "It's an enzyme induced into action to produce nitric oxide during infection, inflammation, or an immune response,” explained Dr. Nathan.