Our current research focuses on identifying genetic factors that contribute to the initiation and progression of neurodegeneration in tauopathies such as Alzheimer’s disease (AD), Frontotemporal dementia with Parkinsonism (FTDP), and Progressive Supranuclear Palsy (PSP). Tau proteins, encoded by the gene MAPT are the main component of neurofibrillary tangles (NFTs); NFTs are pathological lesions found in tauopathies. We are using molecular genetic and molecular genomic techniques to identify MAPT mutations and disease susceptibility alleles in AD, FTDP, and PSP. Functional validation of disease associated MAPT alleles is being performed by creating transgenic animal models that will help elucidate the mechanisms by which MAPT and tau contribute to neuronal cell death and neurological disease. Candidate gene and association studies are also being used to identify additional genetic factors that may contribute to disease onset, neurodegeneration, and phenotypic variability.