Genetic Architecture of Alzheimer’s disease Proteinopathies

Project Narrative Alzheimer's disease (AD) is a major public health problem. Currently there is no effective treatment for AD. Genetic studies aiming to improve our understanding of the pathogenesis of AD and underlying mechanisms may contribute to personalized medicine goals and better therapies and/or preventive measures This study is focused to delineate the genetic basis of two AD-specific proteinopathies, amyloid-beta (Aβ) and pathologic tau, by whole-genome-sequencing. The successful completion of the proposed comprehensive study using biomarkers of two AD-specific proteinopathies in living people with well characterized amyloid-PET and CSF Aβ42/tau datasets along with clinical outcomes of dementia followed by functional studies will make a major contribution to our understanding of the pathogenesis of AD and underlying mechanisms, which may contribute to personalized medicine goals and better therapies and/or preventive measures.