Scientists find new form of prion disease that damages brain arteries

Mar 05, 2010

National Institutes of Health (NIH) scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that does not cause the sponge-like brain deterioration typically seen in prion diseases. Instead, it resembles a form of human Alzheimer's disease, cerebral amyloid angiopathy, that damages brain arteries.

The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAID's Rocky Mountain Laboratories.

Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include or in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.

The role of a specific cell anchor for is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells.

The scientists then exposed those mice to infectious scrapie and observed them for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.

Their study, Dr. Chesebro says, indicates that prion diseases can be divided into two groups: those with plaques that destroy brain blood vessels and those without plaques that lead to the sponge-like damage to nerve cells. Dr. Chesebro says the presence or absence of the prion protein anchor appears to determine which form of disease develops.

The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain. If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer's disease, Dr. Chesebro says.

Explore further: Secret of tetanus toxicity offers new way to treat motor neuron disease

More information: B Chesebro et al. Fatal transmissible amyloid encephalopathy: A new type of prion disease associated with lack of prion protein membrane anchoring. PLoS Pathogens 6(3): e1000800. DOI:10.1371/journal.ppat.1000800 (2010).

add to favorites email to friend print save as pdf

Related Stories

Mutant proteins result in infectious prion disease in mice

Dec 05, 2008

A worldwide group of scientists has created an infectious prion disease in a mouse model, in a step that may help unravel the mystery of this progressive disease that affects the nervous system in humans and animals. The ...

Is there more to prion protein than mad cow disease?

Sep 30, 2008

Prion protein, a form of protein that triggers BSE, is associated with other brain diseases in cattle, raising the possibility of a significant increase in the range of prion disease. Publishing their findings in the open ...

Alzheimer's prevention role discovered for prions

Jul 03, 2007

A role for prion proteins, the much debated agents of mad cow disease and vCJD, has been identified. It appears that the normal prions produced by the body help to prevent the plaques that build up in the brain to cause Alzheimer’s ...

Researchers find new piece in Alzheimer's puzzle

Feb 25, 2009

Yale researchers have filled in a missing gap on the molecular road map of Alzheimer's disease. In the Feb. 26 issue of the journal Nature, the Yale team reports that cellular prion proteins trigger the process by which ...

Recommended for you

Stroke damage mechanism identified

17 hours ago

Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims—and are now searching for drugs to block it.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Caliban
1 / 5 (1) Mar 05, 2010
The good news is, maybe we won't have to wait to either be cooked or frozen out, as the ever-increasing number of emergent, exceptionally lethal diseases may get us first. We can't even seem to find a cure for TB or Malaria- so how can we expect our Med/Pharm combine to put a stop to any of the others?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.