Project Summary / Abstract Core B (Clinical Core) of this NIA U19 Center at the University of Pennsylvania (Penn) Perelman School of Medicine will be crucial to accomplishing the goals of all Projects and other Cores of this multidisciplinary research program. The Penn U19 Center focuses on priorities that address Alzheimer's disease (AD) and related dementias (ADRD) in topic areas of multiple etiology dementias, such as Lewy body (LB) disorders (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease (PD) dementia (PDD). Among ADRD, AD with abundant LB co-pathology is the most common subtype of AD. Hence, AD with LB and Lewy neurite (LN) alpha-synuclein (aSyn) pathologies (AD+aSyn), PDD and DLB together represent the most common forms of aging-related dementias. The overall goals of this new Penn ADRD U19 Center are to elucidate mechanisms of pathological aSyn-mediated progressive neurodegeneration in AD+aSyn versus pure AD (AD-aSyn), and also compared with LBD, as a function of aging and the heterogeneous accumulations of aSyn, tau and amyloid β (Aβ) pathologies that influence different and variable clinical manifestations of these disorders. The aims for Core B are to: (1) recruit, assess and retain research participants with LBD for U19 Projects I-IV; (2) collaborate with Core C for biomarker/biofluid and tissue collection from existing and new Core B LBD participants, and to assess them longitudinally antemortem for as long as possible to optimize clinical-pathological correlations; (3) collaborate with Core A to educate the medical community and general public on LBD and related disorders, and to train the next generation of PD clinical and translational researchers; and (4) collaborate with Core D to contribute high-quality clinical and biomarker data to the Penn Integrated NeuroDegenerative Disease Database (INDD) and facilitate sharing of clinical and biomarker data within and outside of Penn with new and longstanding internal, national and international collaborators.