Clinical Core

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Clinical Core Project Summary The theme of the Penn ADRC is to better understand both the upstream factors and processes that contribute to Alzheimer’s Disease (AD) heterogeneity and the downstream markers critical to characterizing it. The Clinical Core serves as the central node for this thematic mission by deeply characterizing a clinically and demographically diverse cohort (Aim 1). Given the importance of understanding heterogeneity in the context of the entire AD continuum, we will recruit, assess, and longitudinally follow a cohort, the ADRC UDS Cohort, that spans cognitively normal older adults to those with mild dementia. To capture phenotypic diversity and overlap with other neurodegenerative conditions, the cohort includes frontotemporal dementia (FTD), Lewy Body disease, and atypical and early onset AD presentations. In collaboration with the Outreach, Recruitment, and Engagement Core (ORE), recruitment of African Americans, a group poorly represented in AD research, is also a priority and enhances efforts to examine the diversity of factors that contribute to heterogeneity in expression of disease (Aim 3). In the context of the transformation of AD from being defined as a clinical diagnosis to a disease defined by biomarkers, the Penn ADRC embraces the importance of biomarker acquisition and validation. The Clinical Core facilitates these efforts through acquisition of plasma, cerebrospinal fluid, and MRI and PET imaging (Aim 2). These materials and data are obtained in close collaboration with the Biomarker and Neuroimaging Cores and allow for classification of individuals on the basis of the presence or absence of cerebral b-amyloid plaques (A), tau-based neurofibrillary tangles (T), and neurodegeneration (N). Thus, in as many participants as possible, we will obtain biofluid (CSF and plasma) and/or neuroimaging A/T/(N) designation. To capture the role of cerebrovascular disease (CVD) in AD heterogeneity, we will obtain clinical, biofluid, and neuroimaging measures of risk or downstream manifestations of CVD (e.g. white matter hyperintensities). The Clinical Core will also be a source of genetic material and brain tissue obtained in conjunction with the Genomics and Neuropathology Cores, which will be linked to the above biomarker and clinical data. In light of the potential modulating effect on disease risk, phenotype, and resilience versus vulnerability, we will also obtain measures of social determinants of health (SDoH; Aim 4), which potentially will provide a deeper understanding of the role of ethnoracial differences in disease risk and presentation. In addition to the sharing of this rich and diverse dataset and materials with the National Alzheimer’s Coordinating Center (NACC) and with other ADRCs and institutions, the Clinical Core participates in numerous multi-site collaborative clinical research and intervention studies with the goal of advancing care of people with AD/ADRD (Aim 5). Finally, the Clinical Core serves as an important base for training efforts with the Research Education Component to develop the next generation of investigators and clinicians.