Researchers may have pinpointed the cause of Alzheimer’s disease – a rogue protein called amyloid beta (Aß) that forms plaques in the brain.

Dementia-prone mice with low levels of Aß are spared the disease, research reveals. Drugs that reduce this protein in humans may have the same protective effect.

An estimated 15 million people worldwide suffer from Alzheimer’s disease, a progressive, neurodegenerative disease that clouds memory and causes impaired behaviour.

Scientists have long known that clumps or plaques of Aß are present in the brains of Alzheimer’s patients, but the links between the protein and dementia have been unclear. No one was sure if the plaques were a cause or symptom of the disease.

John Disterhoft of the Feinberg School of Medicine at Northwestern University, Chicago, and colleagues studied a strain of Alzheimer’s disease-prone mouse to try to find out. As the animals age, Aß levels rise and their memory declines – the rodents are less able to remember cage mates and learned locations.

But when a key enzyme, called BACE1, is eliminated through genetic engineering, the mice stay dementia free. This enzyme helps to make Aß, explains Disterhoft. Without it, the protein levels stay low and nerve cells stay healthy.

“This is evidence that Aß floating around in the brain can cause cognitive deficits,” says Disterhoft – at least in mice.

As good as it gets

“The mouse model of dementia is about as good as it gets,” says Simon Lovestone of the Institute of Psychiatry in London, “but it’s not perfect.” The rodents develop some, but not all, of the Alzheimer’s hallmarks. Memory loss is less severe than in humans.

Removing the BACE1 enzyme has no noticeable side effects in mice. So drugs that block the enzyme may be safe to use in humans too, says Lovestone. Such drugs already exist, so the next step is to test them in patients. Treatments like this could stave off or even reverse dementia.

The research may also help to settle a long-standing debate. Some Alzheimer’s researchers think that Aß triggers dementia, but others think that a different protein, called tau, causes symptoms.

Amyloid beta may trigger tau build-up, which may in turn cause the disease, says Disterhoft. The next step is to test whether drugs that block BACE1 also prevent tau accumulation.

“I don’t believe this is the last word on the discussion,” says Susanne Sorensen, head of research at the Alzheimer’s Society in London. The study clearly shows the benefits of using genetically modified animals in the research of difficult-to-study neurological conditions such as Alzheimer’s disease.

More here.