New dementia gene discovery
August 2006Researchers from the Divisions of Regenerative Medicine and Medicine and Neurosciences have played a key role in an international collaboration, which has identified a second gene mutation causing a common type of dementia. The researchers were also members of the team that discovered the first gene to be associated with frontotemporal dementia (FTD) in 1998.
The discovery of the connection between FTD and the gene 'granulin' was published in Nature in July, and will open up an entirely new field of biological research. Scientists had not previously suspected this gene was involved in FTD, and the finding will help improve diagnosis of the illness as well as the development of treatments.
Approximately 750,000 people in the UK have some form of dementia, and FTD is second only to Alzheimer's disease amongst younger sufferers. It affects 1 in 5000 people, mostly aged between 50 and 60.
Dr Stuart Pickering-Brown said: "The duration of the illness is often long - seven to ten years is common. During this period the degenerative disease is marked by loss of brain tissue in the front parts of the brain, leading to behavioural and language problems. Sometimes patients also develop symptoms of motor neuron disease or Parkinson's disease in addition to dementia.
"While a lot of progress has been made in understanding the genetic causes of Alzheimer's disease, relatively little was known about the genes linked to FTD. Yet about half of all people with FTD have other family members with the disease.
"From our first findings in 1998 we knew around 10% of cases of FTD are caused by errors in a gene called tau. Now, we know that many more cases probably result from errors in the granulin gene."
In an extraordinary coincidence, both genes are found on chromosome 17. "It is extraordinary that there are two different genes on the same chromosome both causing the same disease," Stuart continued. "Most importantly, as it appears that an actual loss of granulin caused by the mutations leads to FTD, we should be able to develop replacement therapies to effectively tackle this form of dementia."
Professor David Mann added: "We in Manchester are one of the few groups in the world that could do this work. This is a rare disease, so you need large numbers of patients with a family history to discover these genetic changes.
"We have been working on this problem for 20 years and our cohort of patients, built over this time, is possibly the largest and best characterised in the world. This is especially important from a genetics standpoint, in terms of having DNA to analyse from patients in whom the medical characteristics of the illness are fully known."
The team presented the findings in the 'Hot-Topics' session at the International Conference on Alzheimer's Disease and Related Disorders in Madrid in July.
Team members from The University of Manchester
Dr Stuart Pickering-Brown of the Division of Regenerative MedicineProfessors David Mann and David Neary and Dr Julie Snowden of the Division of Medicine and Neurosciences based at Hope Hospital
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