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Prion Found to Damage Brain Arteries

Prion protein plaques around a blood vessel.Chesebro et al.

Scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that doesn’t cause the sponge-like brain deterioration typically seen in these disorders. Instead, they found damage to brain arteries that resembled a disease related to human Alzheimer’s disease.

Prion diseases (also known as transmissible spongiform encephalopathies) are rare, fatal conditions that cause the brain to develop lesions so that it looks like a sponge. They include "mad cow" disease in cattle, scrapie in sheep and Creutzfeldt-Jakob disease in humans.

Previous studies have shown that prion proteins need a specific molecule, glycophosphoinositol (GPI), to fasten to cells in the brain and other organs. Scientists at NIH’s National Institute of Allergy and Infectious Diseases (NIAID), along with collaborators at the Veterinary Laboratories Agency in Scotland, genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby allowing it to diffuse freely in the fluid outside the cells. The scientists then exposed the mice to infectious scrapie and observed them for up to 500 days. The results appeared in the March 5, 2010, edition of PLoS Pathogens.

The researchers saw signs typical of prion disease, including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they didn’t find the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process called cerebral amyloid angiopathy. Cerebral amyloid angiopathy is related to Alzheimer’s disease and involves damage to arteries, veins and capillaries in the brain. The normal pathway by which fluid drains from the brain also appeared to be blocked in the mice.

The results are similar to findings from 2 newly reported cases of the human prion disease known as Gerstmann-Straussler-Scheinker syndrome. The usual prion protein cell anchor was also missing in those cases. Together, these studies represent a new mechanism of prion disease brain damage.

“Our study indicates that 2 types of brain damage occur in prion diseases: abnormal prion protein plaques that destroy brain blood vessels and displace brain tissue, and abnormal prion protein without plaques that leads to the sponge-like damage to nerve cells,” says lead author Dr. Bruce Chesebro, chief of the Laboratory of Persistent Viral Diseases at NIAID’s Rocky Mountain Laboratories. “The presence or absence of the prion protein anchor appears to determine which form of disease develops.”

If scientists can find an inhibitor for the new form of prion disease, Chesebro says, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer’s disease.