Mechanisms of human neurodegenerative diseases My group is using transgenic mouse models to study the mechanisms of human neurodegenerative diseases, particularly AD and PD. There are three broad areas of active interest. Understanding the pathogenesis/progression of PD using alpha-synuclein and LRRK2 transgenic mouse models. Mechanisms of amyloid-dependent neurodegeneration using transgenic mouse models of AD. Pathologic interactions between genetic and environmental factors. While most cases of AD and PD are "sporadic", the key assumption is that genetic lesions that cause classic forms of the relevant neurodegenerative diseases will cause neural abnormalities that are common between the genetic and sporadic forms of the disease. When used in conjunction with careful analysis of human subjects, invertebrate models, and cell culture models, we will be able to define mechanisms that are directly relevant to the pathogenesis and identify possible targets for therapeutic intervention. The models generated are also essential for cross-platform screening and validation of novel therapeutic approaches. My group has identified several robust biochemical, pathological and behavioral outcome measures in transgenic mouse models of AD and PD. These measures will be essential for in vivo preclinical evaluation of therapeutics.
