Alzheimer's is a progressive, terminal brain disease and is the leading cause of dementia. Scientists at the “Carlo Besta" National Neurological Institute in Milan, Italy have discovered a gene mutation that seems to give protection when inherited from only one parent but causes Alzheimer’s when two copies are inherited. Fabrizio Tagliavini, who along with his colleagues, discovered this mutation hope that this research will lead to the development of new drug therapies that can be used to treat both genetic and sporadic forms of the disease.
The gene mutation found occurs in APP, which makes a protein known as A-beta, is often linked to familial cases of Alzheimer’s. Although only a small proportion of the millions Alzheimer’s cases are linked to single, inherited mutations, this particular mutation is unique in that it needs to be inherited from both parents to cause the disease. Most mutations already identified are dominant and require only one copy to produce the disease.
The mutation was discovered in a patient with signs of early onset Alzheimer’s, but no mutations in other genes associated with the inheritable form of the disease. For further research, cells were taken from a 44-year old man with early onset Alzheimer’s that had two copies of the APP mutation. It was found that his A-beta proteins developed clumps more often then cells from people with normal APP gene. One theory for the cause of Alzheimer’s is linked to the development of such clumps.
Relatives of the early onset Alzheimer’s patient with only one copy of the mutant APP gene did not show any symptoms of the disease, including an 88-year old aunt. This was backed up by the observation that when normal and mutant forms of A-beta were mixed together, there were even less clumps than with the normal protein alone. Indicating that inheritance of only one mutant allele of APP may protect a person from Alzheimer’s disease.
Tugliavini and his colleagues hope the creation of a synthetic protein could be used to recreate the mixture of proteins that reduces clumping in patients with two copies of the mutant gene. In fact his team has found a mutant protein that reduces clumping of the proteins. It is only six units long which hopefully increase the chances of successful travel through out the body.
Even if a drug is not developed the APP mutation discovery will change how scientists view the genetics of Alzheimer’s.
Articles:
http://www.newscientist.com/article/dn16750-paradoxical-gene-causes-and-protects-against-alzheimers.html
http://www.sciencedaily.com/releases/2009/03/090312140846.htm
http://www.sciencemag.org.ezproxy.library.uq.edu.au/cgi/content/full/sci;323/5920/1473?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=tagliavini&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
Other Sources:
http://en.wikipedia.org/wiki/Alzheimer's_disease
http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp
