Gene clue to Alzheimer's disease

New research, published last month in the journal Cell, has identified a previously unknown gene, named CALHM1, that is linked with Alzheimer's disease. A certain allele, or version, of this gene, was found to be associated with an increased risk of developing late-onset Alzheimer's. A large international team, led by Dr Philippe Marambaud, of Albert Einstein College of Medicine, New York, and Dr Fabien Campagne of the Weill Medical College Of Cornell University, New York, used bioinformatics, epidemiology and molecular techniques to identify and characterise the gene. The findings shed light on the underlying mechanism of disease in Alzheimer's, and may lead to the discovery of new drug targets for treatment.

Alzheimer's is a progressive neurodegenerative disorder, characterised by loss of memory and personality changes, that eventually leads to death. Late-onset Alzheimer's is the most common form of the disease, and approximately 700,000 people in the UK are affected by it. Although the cause of Alzheimer's is complex and not fully understood, the presence of amyloid plaques in the brain is common to all sufferers. These plaques are made up of clumps of amyloid precursor protein (APP). Previous studies have found a gene, named APOE, that is thought to play a role in clearing the amyloid protein from the brain. The allele APOE e4 is associated with an increased risk of developing Alzheimer's.

The gene discovered in this study, CALHM1, encodes a calcium ion channel protein present on the surface of cells in the brain. It is thought to be involved in controlling the cellular concentration of calcium, which is critical for the regulation of APP processing. The researchers also found that possession of a common allele of the CALHM1 gene (named p86L) results in double the risk of disease. Like the APOE e4 allele, the high risk allele of CALHM1 is also associated with an earlier age of onset of Alzheimer's.

Currently there is no way to prevent or cure Alzheimer's. Researchers hope that discovery of this new gene will increase understanding of the disease, and may provide a good target for drug design. This is because the protein encoded by CALHM1 is on the surface of brain cells, and because its activity is restricted to the brain, drugs aimed at CALHM1 are less likely to have peripheral side effects.

Another group has recently published research showing that an imbalance of calcium is important in forms of the disease that strike early. 'We are very excited about the idea that CALHM1 could be an important target for anti-amyloid therapy in Alzheimer's disease' said Dr Marambaud.