PROJECT SUMMARY The Translational Therapeutics Core (TTC) will provide the infrastructure and expertise necessary to accelerate preclinical development of novel therapeutics for Alzheimer’s disease (AD) and AD-related dementias (ADRD). The TTC will fill a critical void in the development of new therapeutics in the AD/ADRD field by facilitating 2 critical components of translational science that are desperately under supported in academia: (1) human target validation of basic science findings, and (2) network medicine approaches to identify already existing agents for drug repurposing. A critical aspect of this is human data towards target validation, through the realms of clinical experience, human genetics, and tissue expression. This is particularly logistically challenging in the field of AD/ADRD due to scarcity of quality tissue and disease complexity. Through the establishment of the Cleveland Alzheimer’s Disease Research Center (CADRC) Cores, the TTC will work closely with the Biomarker Core (BC) to provide not only access to deeply phenotyped biological samples, but expert guidance in the heterogeneity of ADRD. The TTC will bring to the CADRC a wealth of shared resources including the Harrington Discovery Institute (HDI) at University Hospitals, which is part of the Harrington Project for Discovery & Development, an international initiative designed to enable inventive scientists to advance their discoveries into novel medicines that will improve human health by providing funding and drug development support to bridge the gap between basic discovery and the clinical realm. The TTC is led by Dr. Andrew Pieper, Director of the Alzheimer’s Drug Discovery Foundation (ADDF) – Harrington Scholar Program, which supports scientists to develop drugs that will prevent, treat, and cure AD/ADRD. The TTC will identify and support researchers developing therapeutics currently targeted for AD/ADRD locally in the CADRC, and nationally and internationally through Dr. Pieper’s relationship with ADDF and HDI (Specific Aim 1). Researchers who have developed preclinical support for novel hypotheses related to AD/ADRD will be supported through Dr. Cheng’s methods for network-based approaches to identify drugs that might be repurposed for treating AD/ADRD. The TTC will also apply the same principles as in Specific Aim 1 to support researchers developing novel therapeutics or hypotheses in other areas of medical research that might also be applied to AD/ADRD, in order to support critical diversity of innovation for developing new treatments for AD/ADRD (Specific Aim 2). In addition, coordination with the CADRC Biomarker Core (BC) will enable the TTC to facilitate identification of markers related to new therapeutic approaches, which might be applied in future clinical trials or patient care. By providing access and funds for target validation in human tissue using the growing biospecimen collections in the CADRC Biomarker and Neuropathology Cores, the TTC will ...