ABSTRACT: OVERALL The University of Kansas Alzheimer's Disease Research Center (KU ADRC) promotes Alzheimer's Disease and Related Disorders (ADRD) research at local, national, and international levels. Our strengths in basic and translational mitochondria, lifestyle modification, and prevention research define a metabolism theme we pursued and refined over the past decade. We boast a sophisticated and mature infrastructure that advances a better understanding of AD, better care of affected persons, and new treatment interventions. The KU ADRC will use its intellectual and infrastructure assets this next cycle to drive AD research at a university vested and investing in our success, and in doing so move the field closer to a cure. Our Center moves seamlessly between bench and bedside, both in terms of the research projects we support, and in the infrastructure required to back investigator projects. Lifestyle intervention research generates fundamental mechanistic questions we call on wet lab investigators to address, and questions of clinical implementation and practice are now the focus of dry lab, clinical, and health care delivery investigators. Research addressing AD's mitochondrial component demonstrate a role for mitochondrial genes in AD risk, that mitochondria play a critical role in cell proteostasis and protein aggregation, specific links between mitochondria and AD hallmark proteins, and how to manipulate brain energy metabolism through lifestyle and pharmacologic approaches. To date these efforts led us to create novel compounds that constitute a unique therapeutic pipeline, and clinical trial infrastructure that supports actual studies of metabolism interventions in actual AD patients. For the 2021-26 cycle we will use our intellectual and infrastructure assets to address critical gaps in the AD field, including gaps in fundamental knowledge and care implementation. During this cycle the KU ADRC will work to (1) Empower innovative AD and brain aging research, education, and clinical programs; (2) Drive field-defining metabolism research, and (3) Bring practical and novel metabolism-directed therapies to the bedside and clinic.