ABSTRACT: BIOMARKER CORE The Biomarker Core performs fluid biomarker assessments for the University of Kansas Alzheimer's Disease Research Center (KU ADRC). For Cohort participants we determine amyloid-tau-neurodegeneration (ATN) levels in cerebrospinal fluid (CSF) and plasma; measure plasma inflammation, neurotrophin, and metabolism-relevant endpoints; and obtain blood and brain mitochondrial DNA (mtDNA) sequences. In addition to meeting the Center's need for standard ATN biomarker assessments, the Biomarker Core maintains the innovation and unique resources of our foundational Mitochondrial Genomics and Metabolism (MGM) Core. The MGM Core developed novel mitochondrial and metabolism biomarkers and used those biomarkers as clinical trial target engagement endpoints. It also identified mitochondria and metabolism- associated diagnostic and prognostic biomarkers. The original MGM Core also offered state-of-the-art consultation and technical support to investigators and here the Biomarker Core delivers these services. Cell models available through the MGM Core including cytoplasmic hybrid (cybrid) cell lines, induced pluripotent stem cell (iPSC) lines, neurons and glia differentiated from iPSCs, and lymphoblast cell lines remain available through the Biomarker Core. Adding ATN assessments enriches our Clinical Cohort dataset and nurtures an emerging ADRD field-wide interest in correlating ATN biomarkers with mtDNA signatures, mitochondrial function, and energy metabolism. Extending these services to investigators benefits their research projects and programs. It provides our local, national, and international users the much-valued metabolism-oriented service, expertise and reagents we provided during our previous two cycles. It maintains our preeminence in understanding the causes of AD mitochondrial and energy metabolism dysfunction, the consequences of that dysfunction, and how to manipulate mitochondria and energy metabolism with therapeutic or prevention intent. During this cycle the Biomarker Core will accomplish its goals by focusing on the following Specific Aims: (1) Perform fluid and tissue biomarker assessments; (2) Pursue mitochondrial and metabolism biomarker development; and (3) Provide cell models, technical services, and novel biomarkers.