Alzheimer's clue

Canadian researchers have excised another clue as to the cause of the debilitating brain disorder Alzheimer's disease. The discovery might one day lead to a new class of drug that blocks the build up the beta-amyloid-peptide in the brain that leads to progressive memory loss, speech problems, delusions and immobility.

Peter St. George-Hyslop, a geneticist and molecular biologist at the University of Toronto and his team discovered that two different mutations in the presenilin gene are involved in a particular hereditary form of AD. The mutations were always associated with high levels of a peptide known to cause the neurofibrillary plaques and fibrous tangles lead to neuronal cell death and the symptoms of the disease. The picture was not entirely clear though and explaining how the peptide has its toxic effects and why the brain cannot flush it out have remained something of a mystery.

Writing in Nature (2000, 407, 48) St George-Hyslop and his colleagues describe the protein trigger that may be responsible for releasing the peptide into the brain. They have named it nicastrin, after the Italian village where pioneering work into AD has been conducted. Nicastrin, is thought to be involved in fetal development but seems to regulate the formation of the toxic peptide. A manipulation of a small band on the nicastrin protein allowed the team to control just how much peptide is formed, making nicastrin an obvious drug target. It will inevitably be several years before the research bears fruit in the form of a drug to treat the disease rather than the symptoms.

AD affects hundreds of thousands of people worldwide and some estimates have it that the number of victims will double over the next 30 years.AD affects hundreds of thousands of people worldwide and some estimates have it that the number of victims will double over the next 30 years.