Effect of Novel ADAM10 Gene Mutations in Alzheimer's Disease
MentorRudolph Tanzi, PhD Massachusetts General Hospital
In this study, we are exploring the idea that newly discovered Alzheimer's disease associated mutations in the Alzheimer's diseaseAM10 gene attenuate the function of ADAM10. This is being accomplished by generating and characterizing genetically modified mice over-expressing either wild-type or mutant forms of ADAM10. We are also assessing the effects of these mutations on Alzheimer's disease-like characteristics in a mouse model of the disease.
Alzheimer's disease is one of the leading causes of death and the most common form of dementia in the elderly. As the average life span is extended, the number of patients suffering from this disease is increasing dramatically, placing a huge burden on our healthcare system and on our global society. The incidence of Alzheimer's disease increases with age and doubles every five years after age 60. Currently there exists no effective treatment to stop or slow the progression of this devastating disease. Although an enormous amount of effort and resources have been devoted to research and clinical trials aimed at finding effective therapeutic interventions, the cause of this disease remains unclear. In this study we are attempting to validate our genetic findings from Alzheimer's disease families using a transgenic mouse model system. The novel mutations were found in the ADAM10 gene and can increase the production of neurotoxic peptide, called amyloid beta, which is considered a major factor for Alzheimer's disease progression. The results from this study can provide critical in vivo evidence for the cause of late-onset Alzheimer's disease. Moreover, the data emerging from this study would also serve as a firm foundation for the discovery and development of new drugs targeting ADAM10 for the treatment and prevention of Alzheimer's disease.