Analysis of Mitochondrial Genetics, Family History and Brain Imaging data in 
   Lead Investigator:    Robyn Honea
   Institution      :    University of Kansas
   E-Mail           :    rhonea@kumc.edu
   Proposal ID      :    1610



   Proposal Description:
   Individuals with a maternal family history of Alzheimer???s disease (AD) have a  substantially (3-9 times higher) increased risk of AD compared to individuals     with a paternal or no family history of AD, however we still do not understand   why a maternal family history imparts more risk. First, we will use family       history of AD to investigate the role of mitochondrial genetic variation in AD,  and second, we will use brain imaging phenotypes that have been identified as     risk markers for AD. Previous work supports our choice of family history of AD   and AD-specific brain imaging phenotypes as proxy-phenotypes.                     Aim 1: Conduct association studies within the mitochondrial genome using family  history of AD as a proxy-phenotype.                                               Aim 2: Conduct association studies within the mitochondrial genome using brain   structural/metabolic changes as a proxy-phenotype for AD.                         Our proposal is designed to determine if mitochondrial genetic variation is       contributing to familial transmission of AD and identify if these variations     result in changes in the brain detectable by imaging. The variants we             anticipate identifying are different than previously reported mitochondrial       genomic variants and may illuminate the role of mitochondrial genomics in AD     and provide insights into the etiology of AD. Therapeutic treatments to restore  mitochondrial function and metabolism (e.g. mitochondrial gene therapy,           embryonic mitochondrial DNA transplantation, stem cell therapies,                 pharmacological intervention, etc.) have been applied in numerous complex human  diseases, but treatments that specifically target the mitochondria have not       been developed for AD. The results from our analyses will identify novel         therapeutic targets for AD, thus providing the foundation for successful         intervention in AD.