New Prion Disease Damages Brain Arteries

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Main Category: Neurology / Neuroscience
Also Included In: Alzheimer's / Dementia;  Vascular;  Veterinary
Article Date: 05 Mar 2010 - 9:00 PDT

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A team of scientists from the US and the UK have found a new type of prion disease in mice that damages brain arteries and may help us better understand and treat types of Alzheimer's disease that cause similar damage.

You can read a scientific paper about the discovery in the 5 March online issue of the journal PLoS Pathogens.

First author Dr Bruce Chesebro, chief of the Laboratory of Persistent Viral Diseases at the Rocky Mountain Laboratories of the US National Institute of Allergy and Infectious Diseases, told the press that they found a mechanism of prion disease brain damage not seen before.

He said if scientists could develop an inhibitor for the new type of prion disease, it might be possible to use it to treat similar damage in Alzheimer's disease.

Prion diseases, also called transmissible spongiform encephalopathies, are brain wasting diseases that affect humans and animals. Made primarily of protein, prions are small active agents that act a bit like viruses: they don't replicate themselves but hijack material in the host and cause it to behave abnormally, for instance they force host proteins to fold into shapes that clump together into plaques that clog up the brain, causing it gradually to waste away.

There are different types of prion diseases, for instance in humans they include sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and Gerstmann -Straussler-Scheinker syndrome (GSS), and in animals they include mad cow disease (bovine spongiform encephalopathy), scrapie in sheep, and chronic wasting disease in deer, elk and moose.

Most of them are characterized by the sponge-like matter (gray matter spongiosis) of the plaques accumulating in the brain.

But in this study, Chesebro and colleagues observed that the disease looks more like the damage seen in a type of human Alzheimer's disease, caused by a process called cerebral amyloid angiopathy that destroys brain arteries. They said what they found was also similar to the type of damage found in two newly reported cases of GSS.

For the study, the researchers concentrated on the role of a cell anchor for prion protein. Normally, prion protein uses a GPI (glycophosphoinositol) molecule to fasten itself to a host cell, but when they genetically removed the GPI anchor from prions in lab mice, Chesebro and colleagues noticed that they diffused freely in the fluid surrounding the cells rather than anchoring to them.

They then exposed the mice to infectious scrapie and monitored them for up to 500 days. The mice got sick and developed symptoms of prion disease such as they became inactive, they lost weight, stopped grooming themselves and moved abnormally.

When they examined the brains of the mice the researchers did not find the usual sponge-like holes in and around the nerve cells. Instead, they found large clumps of prion protein formed outside of blood vessels, which is what happens in cerebral amyloid angiopathy.

They also found that the path normally used to drain fluid from the brain was blocked.

Chesebro said the findings suggest there are two types of prion disease: one that produces plaques that result in the sponge-like damage, and the other that damages arteries, depending on whether the prion protein has the anchor or not.

The prion proteins found in the two recently reported human cases of GSS also lacked the cell anchor, and Chesebro said that these cases, together with the genetically engineered mice used in their study, are the first examples to show that prions can damage the blood vessels in the brain without producing the sponge-like result.

"Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring."
Bruce Chesebro, Brent Race, Kimberly Meade-White, Rachel LaCasse, Richard Race, Mikael Klingeborn, James Striebel, David Dorward, Gillian McGovern, Martin Jeffrey.
PLoS Pathogens, published online 05 Mar 2010
DOI:10.1371/journal.ppat.1000800

Sources: NIH/National Institute of Allergy and Infectious Diseases.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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