The University of Pittsburgh Alzheimer?s Disease Research Center (PITT- ADRC) has shown a clear scientific evolution over the past three decades. Since our inception, we have advanced the areas of AD neuropsychiatry, genetics, natural history of AD, validation of clinical criteria, and clinico-pathological correlations, and have pioneered the development of PET amyloid tracers, which have transformed AD research. We have used a multidisciplinary approach to better understand the transition from normal cognition to dementia, have explored the biology of more aggressive forms of AD characterized by psychosis, and have made and contributed to new insights in genetics. This solid scientific background and investment in junior investigators has allowed the PITT-ADRC to develop areas of excellence, which form the foundation of our Center going forward. These are reflected in the Center?s cores, and most notably in the large number of studies we support in these areas in Pittsburgh and at national and international level. The PITT-ADRC is committed to remain at the forefront of the scientific efforts to understand the pathological processes involved in the etiology of AD. Along with the high level of research conducted by the PITT-ADRC, we are also dedicated to developing strong training programs to promote the careers of young investigators, consolidate the career of midlevel investigators, and to create strong ties with the community through educational and support programs. The PITT-ADRC is highly committed to leverage the strengths of the network of Centers to provide large numbers of samples and standardized clinical data collection from our participants. The PITT-ADRC has designed novel methodology that improves the accessibility of its database to local and national researchers, and it has been a key player in multiple studies that advanced the understanding of AD pathology and its possible implications for the development of novel treatments and other symptoms. Therefore, we provide an excellent environment that enhances cutting-edge research by bringing together a multidisciplinary team of investigators to study AD and other dementias, and to improve health care delivery. The methodology proposed in this application will lead us to the creation of a unique and well-characterized cohort of patients and normal control subjects assessed with state of the art clinical and biomarker methods. This will allow us to test multiple scientific hypotheses and to examine the short- and long-term public health outcomes of the pathophysiology of cognitive disorders in the adult. We believe that the PITT -ADRC will be at the center of the new era of AD research that will require a wealth of clinical and biological data, highly sophisticated biomarker methodologies, close inter-relationship among centers and institutions, creation and optimization of human resources, and enhanced communication with patients and families.
Neuroimaging Supplement Abstract/Narrative: The overall goal of the PITT-ADRC is to perform and promote research that increases our understanding of: 1) the etiology and pathogenesis of Alzheimer's disease (AD), 2) the mechanisms underlying the cognitive and behavioral symptoms of AD, and 3) to develop strategies that will result in effective early diagnoses and treatments for AD and related dementias. The Neuroimaging Core (NIC) will support these Center-wide goals by developing and applying cutting edge neuroimaging technology to studies that are focused on early and presymptomatic stages of the AD spectrum. As the search for preclinical biomarkers continues, it is becoming increasingly clear that functional and structural brain imaging data may hold the key to identifying the earliest pathological manifestations of AD prior to any meaningful clinical change. The NIC will continue to develop and distribute technology for acquiring and interpreting brain functional and structural imaging data in the support of AD research. The NIC will advance the Center goals by supporting and promoting research that increases our understanding of the etiology and pathogenesis of AD and facilitates the development of new therapies and methods for monitoring therapeutic efficacy. The NIC maintains data sets of structural imaging on individuals enrolled through the Clinical Core, and we continue to work on the expansion of leading edge analytic technologies, and novel radiotracer ligands measured with Positron Emission Tomography (PET) (i.e., PiB, AV-1451, and GTP-1). The present revision of the NIC seeks to add MK-6240 tau PET imaging for additional head to head comparisons, to develop z-scores and a standardized mask for a ?centiloid-style? scoring. The proposed work will accelerate efforts to standardize tau PET imaging by establishing a methodology for a standardized quantitative tau PET measure and by providing head to head comparison data from 3 tau PET ligands to the SCAN initiative for public use.
