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    Researchers at Massachussets General Hospital have found two gene mutations that may cause common form of Alzheimer's, which manifests after age sixty.  The mutations are in a gene called ADAM10, an enzyme previously linked to the amyloid precursor protein processing.
    The report, which will be published October 16th in Neuron, explores how the mutations affect the growth and toxicity of amyloid in a mouse model.  The research also shows that these mutations affect the hippocampus's ability to create new neural cells, which are imperative to learning and memory.  Dr. Rudolph Tanzi, director of Genetics and Aging Research at Massachussets General, says that their pinpointing of the pathological gene mutations add to the only previous discovery of other mutations.  Tanzi also says the study's result show that lowered ADAM10 activity can cause Alzheimer's.
    Amyloid beta forms its characteristic plaques when the amyloid precursor protein (APP) is shortened by enzymes called secretases.  APP is progressively processed by beta-secretase and subsequently gamma-secretases resulting in amyloid beta peptide that may oligomerize resulting in toxic species.  ADAM10 is the alpha-secretase that can alternatively process APP that prevents processing by Beta-secretase resulting in into peptides that stimulate neural growth.  
    Tanzi's team went about studying how mutations in ADAM10, a helpful molecule, could heighten the likelihood of developing Alzheimer's disease.  Transgenic mice experiments showed the scientists four things; mutations lowered the brain's release of beneficial proteins, reduced ADAM10 activity caused increased generation of amyloid beta, a mutation-caused reduction in ADAM10 impaired the ability of the hippocampus to generate new neurons, and the mutations achieve these destructive powers by changing the correct folding of ADAM10 to interfere with its normal funcntions.  Scientists belive that this new research regarding the importance of ADAM10 and alpha-secretase in Alzheimer's disease will allow for new treatment options and research.     
Source:
1) Massechussets General Hospital (September 24, 2013). Rare Mutations Increase Risk of Late-Onset Alzheimer's Disease.  Science Daily.  Retrieved September 26, 2013, from http://www.sciencedaily.com/releases/2013/09/130924113454.htm
Keywords: Alzheimer's, ADAM10, alpha-secretase

By Emma Henson

Roskamp Institute is a non-profit research institute located at Sarasota, FL. The mission of the institute is identify cure for Brain related disorders. Dr. Michael Mullan is the head of the institute. He discovered Swedish mutation in APP gene.

 


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