'The Bad Guy' Protein That Triggers Alzheimer's Disease Discovered

PA/The Huffington Post UK  |  Posted: 2/05/2012 18:31 Updated: 2/05/2012 18:31

A highly-toxic protein described as the "real bad guy" behind Alzheimer's disease has been identified by scientists.

The molecule recruits other less harmful proteins and makes them deadly to brain cells.

Knowing how it forms and behaves is expected to lead to more effective Alzheimer's treatments.

One experimental drug to emerge from the research has already completed early phase I clinical trials. The protein is a special type of beta-amyloid, which was already known to play a key role in Alzheimer's.

Beta-amyloid clumps together in the brains of Alzheimer's patients, forming deposits that result in the destruction of nerve cells.

"This form of beta-amyloid, called pyroglutamylated (or pyroglu) beta-amyloid, is a real bad guy in Alzheimer's disease," said lead scientist Professor George Bloom, from the University of Virginia in the US.

"We've confirmed that it converts more abundant beta-amyloids into a form that is up to 100 times more toxic, making this a very dangerous killer of brain cells and an attractive target for drug therapy."

He compared the way the protein spread destruction in the brain to the transmission of prion diseases, such as Creutzfeldt Jakob Disease (CJD).

Prion diseases are caused by rogue misshapen proteins that toxify other proteins they come into contact with in a chain reaction.

"You might think of this pyroglu beta-amyloid as a seed that can further contaminate something that's already bad into something much worse - it's the trigger," said Prof Bloom.

The research is published today in the latest online edition of the journal Nature.

Prof Bloom's team also looked at interactions between beta-amyloid and tau, another Alzheimer's-related protein.

Mouse experiments confirmed that both beta-amyloid and tau were needed to trigger the destruction of nerve cells.

"There are two matters of practical importance in our discovery," said Prof Bloom.

"One is the new insights we have as to how Alzheimer's might actually progress - the mechanisms which are important to understand if we are to try to prevent it from happening; and second, it provides a lead into how to design drugs that might prevent this kind of beta-amyloid from building up in the first place."

Co-author Dr Hans-Ulrich Demuth, chief scientific officer at the German biotech company Probiodrug, said: "This publication further adds significant evidence to our hypothesis about the critical role pyroglu beta-amyloid plays in the initiation of Alzheimer's disease."

Probiodrug, based in Halle, has completed phase I safety trials of a drug that suppresses an enzyme involved in the formation of pyroglu beta-amyloid.

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