The Penn U19 Center consists of four Cores that support two experimental and two patient-oriented Projects.
Core A - Administrative Core
Core A Leader: Virginia M.-Y. Lee, PhD
Core A facilitates accomplishing the goals of this multidisciplinary Penn U19 Center research program. Accordingly, the Aims of Core A are to oversee budgetary and fiscal aspects of this Center; promote/foster interactions between Cores and Projects, as well as interactions of Penn U19 investigators with scientists outside the U19 Center at and beyond Penn.
Core Members: Kathy Jedrziewski, Administrator and Carl Jamison, Senior Grants Manager
With our goals in mind, Core A aims to:
- Convene U19 External Advisory Committee meetings
- Serve as an information resource for outreach to the patient community and general public regarding AD+aSyn, LBD and MSA
- Monitor progress of Cores/Projects
- Facilitate sharing of data/reagents/resources of the Penn U19 Center with other researchers in partnership with the NIA
- Participate in national and international meetings on ADRD as well as Penn symposia to accelerate the pace of advances in understanding ADRD and related synucleinopathies as well as promote outreach to the public
- Train the next generation of AD+aSyn and LBD investigators and enhance the careers of junior faculty
- Host and train outside investigators who wish to visit our Center to learn methods required for transmission studies of pathological tau and aSyn.
An Internal Executive Committee (IEC) composed of Core and Project Leaders will work with NIA to respond to and adjudicate applications for U19 resources and data.
Core A plays a key role in the mission of this U19 Center with considerable institutional support, as described in Core A and in letters of support from the University of Pennsylvania Perelman School of Medicine (PSOM) Dean Larry Jameson, Vice Dean for Research Jon Epstein and other PSOM leadership.
Core B - Clinical Core
Core B Leader: Daniel Weintraub, MD
Core B recruits and evaluates patients with LBD and supports assessments of AD patients through the Penn AD Core Center (ADCC), some of whom will have AD+aSyn on autopsy, for research conducted by the U19 Center’s Projects.
Co-Investigators: Alice Chen-Plotkin, Nabila Dahodwala, David Irwin, James Morley, Andrew Siderowf, Allison Willis and David Wolk
Core B is an essential link to the other Cores for collaborative studies and support of education, outreach, training and career enhancement, collection of blood (for DNA extraction and plasma biomarkers), CSF, structural MRIs, and brain tissue/DNA, and data collection, biostatistics and management (see Core D).
Core B will use NINDS Common Data Elements (CDEs) and components of ADNI and NACC DLB assessment protocols for collection of clinical and cognitive data, and work with NIA to send biosamples to qualified investigators outside the U19 who are approved through mechanism described in Core A and the instructions for sample access, work with Core D to upload all data to the Penn Integrated Neurodegenerative Disease Database (INDD), and collaborate with the ADCC and other AD and LBD focused research programs on multi-center studies.
The PD Research, Education and Center (PADRECC) at the Philadelphia Veterans Affairs (VA) Medical Center is an integral part of Core B. This PADRECC is one of 6 VA Centers of Excellence specializing in the diagnosis and management of PD and related movement disorders, and it offers clinical, research, and educational services for Veterans, 20% of whom are minorities. Thus, this PADRECC adds racial and socioeconomic diversity to our U19 Center.
Core C - Neuropathology, Biomarker & Genetics Core
Core C Leader: Edward B. Lee, MD, PhD
The Neuropathology, Biomarker & Genetics Core C supports the mission of the Penn U19 Center by banking and characterizing postmortem brain tissue from clinically assessed AD and LBD cases, some of whom will have pure AD and MSA, respectively, at autopsy as well as banking biofluids and extracting DNA for studies.
Co-Core Leaders: Alice Chen-Plotkin and Vivianna Van Deerlin
Core C supports the U19 Center goals by implementing postmortem diagnostic criteria for all subjects followed in Core B who come to autopsy using state-of-the-art methods, while also assessing the utility of antemortem diagnostics, including studies of potential genetic, biofluid and structural imaging signatures.
Core C also works closely with the Projects to identify the best cases for isolation of pathological aSyn from postmortem brains associated with detailed phenotypic data to enable correlations of pathological aSyn stains with subtypes of AD and LBD. To accomplish this, Core C works closely with all Center Cores/Projects by improving diagnostic methods and providing thoroughly characterized fresh, unfixed frozen and fixed CNS tissues, biofluids and DNA to investigators at and beyond the U19 Center in partnership with NIA program.
Core C - Aims: Watch Now
Core C - Importance of Biosamples: Watch Now
Core C - Collaboration: Watch Now
Core C - Data Sharing: Watch Now
Core D - Data Management, Biostatistics & Bioinformatics Core
Core D Leader: Sharon Xie, PhD
Core D is responsible for maintaining a relational database of demographic, clinical, genetic, biomarker, imaging and neuropathology data gathered by the Center. The Center database is linked with the Integrated Neurodegenerative Disease Database (INDD) developed by Xie et al141 which allows cross disease comparative studies with other neurodegenerative diseases such as AD with and without LBs followed in other NIH-funded studies.
Core Investigator: Li-San Wang
Core D provides database, computing, biostatistical and bioinformatics support to Center investigators as well as to outside collaborators with the Center, including data sharing between the Penn U19 Center and the NIA funded AD Centers (ADCs) and NINDS-funded Udall centers and other qualified investigators. It provides biostatistical training to the next generation of ADRD researchers.
The Penn Alzheimer’s Disease Core Center (ADCC) has a National Alzheimer’s Coordinating Center (NACC) DLB Module led by Dave Irwin that will foster collaborations between the U19 Center and the ADCC. It also has a NACC Frontotemporal Degeneration (FTD) Module led by Murray Grossman so there is extensive cross-talk between investigators in this U19 and the Penn ADCC.