Genome-wide study links four new genes to Alzheimer's

A study examining the genomes of more than 1,300 families has revealed four new genes potentially linked to the most common late-onset form of Alzheimer's disease, according to a study published in the American Journal of Human Genetics last week. The researchers, based at the Massachusetts General Hospital - Mass. General Institute for Neurodegenerative Diseases (MGH-MIND), hope that the findings could provide the starting point for finding new and improved ways of diagnosing and treating the condition.

'Virtually all current research into therapies is based on the Alzheimer's genes that we already know about; so each new gene we find not only enhances our ability to predict and diagnose the disease, but also provides valuable new clues about biochemical events and pathways involved in the disease process,' said Dr Rudolph Tanzi, director of the MGH-MIND Genetics and Aging Research Unit, who co-led the study.

Alzheimer's is a progressive neurodegenerative disorder, characterised by loss of memory and personality changes, which eventually lead 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. In the search for genes linked to late-onset Alzheimer's disease, the researchers scanned the genomes of 400 families, in which at least three family members had developed the condition.

Out of the 500,000 genetic markers analysed, five were associated with Alzheimer's disease. One of the five genes associated was APOE (Apolipoprotein E), a gene identified in previous studies which is thought to play a role in clearing the plaques from the brain, which build up in Alzheimer's patients. To confirm the four remaining sites, the researchers scaled up their study, analysing samples from an additional 900 families. The most strongly associated gene was located on chromosome 14 in the vicinity of a gene called presenilin-1, which is thought to play a role in early-onset Alzheimer's disease.

'The genetic association of Alzheimer's with this novel chromosome 14 gene, which like APOE appears to influence age of onset, is sufficiently strong to warrant intensive follow-up investigations into its role in the process of nerve cell death in this disease,' Tanzi said.

Another of the genes identified is know to cause the neurological condition 'spinocerebellar ataxia', which, like Alzheimer's disease, involves the death of nerve cells at key areas in the central nervous system. The remaining two genes are thought to play a role in the immune system and in maintaining functional synapses, the loss of which is linked to dementia in Alzheimer's disease.