Post by Anodyne on Jan 15, 2007 12:22:35 GMT -5
The long-suspected link between Alzheimer’s disease and abnormalities in the way amyloid protein is processed in the brain has been confirmed at last – a significant step on the path to an effective drug treatment for the condition.
Usually harmless, the amyloid precursor protein is thought to trigger neurological damage when it is broken down and transformed into toxic fragments of beta-amyloid. Previous studies have shown that people with Alzheimer’s have reduced levels of several proteins involved in processing amyloid.
To find out whether low levels of any of these proteins could cause the production of toxic beta-amyloid, Peter St George-Hyslop at the University of Toronto in Canada and colleagues studied the DNA of 6861 people, 46% of whom had had Alzheimer’s.
Those with the disease proved significantly more likely to have mutations in the gene SORL1, which usually produces a protein that binds amyloid and transports it to an area of the cell where it can be harmlessly recycled.
To demonstrate that mutate variations in SORL1 could trigger the disease, the researchers treated cells in the lab to deactivate the gene. This, they found, led to a substantial increase in the production of toxic beta-amyloid. “Where SORL1 is absent or defective, it allows the amyloid to float off into other areas where it is degraded,” says St George-Hyslop.
The team have identified two regions of SORL1 which they believe harbour the disease-causing mutations, but have not yet found the mutations themselves. When they do, they hope this will lead them to a drug that increases SORL1 activity in people with variant forms of the gene.
www.newscientist.com/article/dn10955-genetic-search-closes-in-on-alzheimers-mutation-.html
Usually harmless, the amyloid precursor protein is thought to trigger neurological damage when it is broken down and transformed into toxic fragments of beta-amyloid. Previous studies have shown that people with Alzheimer’s have reduced levels of several proteins involved in processing amyloid.
To find out whether low levels of any of these proteins could cause the production of toxic beta-amyloid, Peter St George-Hyslop at the University of Toronto in Canada and colleagues studied the DNA of 6861 people, 46% of whom had had Alzheimer’s.
Those with the disease proved significantly more likely to have mutations in the gene SORL1, which usually produces a protein that binds amyloid and transports it to an area of the cell where it can be harmlessly recycled.
To demonstrate that mutate variations in SORL1 could trigger the disease, the researchers treated cells in the lab to deactivate the gene. This, they found, led to a substantial increase in the production of toxic beta-amyloid. “Where SORL1 is absent or defective, it allows the amyloid to float off into other areas where it is degraded,” says St George-Hyslop.
The team have identified two regions of SORL1 which they believe harbour the disease-causing mutations, but have not yet found the mutations themselves. When they do, they hope this will lead them to a drug that increases SORL1 activity in people with variant forms of the gene.
www.newscientist.com/article/dn10955-genetic-search-closes-in-on-alzheimers-mutation-.html
