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Last Updated: Thursday, 31 July, 2003, 04:19 GMT 05:19 UK
Gene fault 'leads to Alzheimer's'
Protein tangles form in the brains of Alzheimer's patients
Scientists have discovered how the faulty production of an enzyme can lead to the development of Alzheimer's disease.

The enzyme helps proteins called tau support the network of nerve cells in the brain.

In healthy brains, the strands are part of a "scaffolding" system which supports the cells.

But in the brains of Alzheimer's patients, strands of protein bind together to develop tangles in the brain.

The researchers, from Beth Israel Deaconess Medical Center and the Harvard Medical School, have discovered this tangling occurs because of a genetic fault in the gene which controls the enzyme, which is called Pin1.

The discovery could help prevent people developing Alzheimer's, they say.


In a healthy brain, phosphates are added and removed from tau.

But in Alzheimer's, too many phosphate molecules are added, so the protein changes shape and clusters into fibres.

It provides hope for people with Alzheimer's and their families
Dr Susanne Sorensen, Alzheimer's Society
These become tangled and knotted, forming rigid structures that eventually lead to the destruction of the affected nerve cells in certain areas of the brain, resulting in symptoms of dementia.

The US researchers compared Pin1 expression in different areas of the brains in healthy people with those of Alzheimer's patients.

In Alzheimer's patients a faulty gene was linked to formation of the tau tangles, and in healthy patients it showed they were vulnerable to neurodegenerative disease.

They also created a genetically modified mouse which lacked the key gene.

The mouse then experienced many age-dependent neurodegenerative changes.

Dr Kun Ping Lu, the biologist who led the research, said: "We've now shown that Pin1 plays a pivotal role in protecting against age-dependent neurodegeneration.

"This makes a convincing case that this enzyme should be taken into consideration in future studies of Alzheimer's disease."

He added: "Pin1 represents a new category of genes whose expression is required to guard against age-dependent neurodegeneration.

"We now need to conduct further studies to explore why Pin1 expression is low in certain vulnerable neurons, to understand the relationship between Pin1 and other genes that are known to be involved in Alzheimer's disease, and to find ways to increase Pin1 expression.

"Answering these questions could lead to the development of therapies to prevent or slow age-dependent neurodegenerative processes."

The researchers also found that Pin1 works too hard in many human cancers.

They say this over-expression is critical for tumours to develop in the first place.


Dr Susanne Sorensen, head of research at the UK's Alzheimer's Society, told BBC News Online: "Alzheimer's disease is likely to be a multi-factorial disease with the involvement of more than one gene and disease causing mechanism.

"More research is needed to work out the mechanism for this particular enzyme's action and to identify therapeutic targets.

She added: "This type of basic research on the causes of Alzheimer's disease is very important.

"It provides hope for people with Alzheimer's and their families that in the future it will be possible to treat the disease in earlier stages than is presently possible."

The research is published in the journal Nature.

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