PROJECT SUMMARY - BIOMARKER CORE (CORE G) The Biomarker core (BMC) of the Wisconsin ADRC represents the capability and infrastructure for assessing the brain quantitatively in vivo using biofluid and imaging biomarkers of Alzheimer’s disease (AD) and related disorders. A major focus of our center’s investigators is the pre-clinical and early symptomatic stages of AD, and on understanding factors that influence proteinopathy onset and eventual clinical expression. The charge of this core is to provide the necessary tools and infrastructure to our center’s investigators to characterize as accurately as possible the in vivo changes of AD across its stages, the effect of risk and resilience factors that hasten or slow development of symptoms, and the assessment of co-pathology and associated joint impact on clinical course. The Core will focus on collecting and curating several types of robust and exploratory biomarkers including: 1) markers indicative of AD defined by amyloid plaques (A) and neurofibrillary tangles (T) from molecular PET imaging, CSF, and blood-based assays; 2) markers of cerebrovascular diseases (V) —the second most common set of causes of cognitive decline that are ascertainable by both well-established and novel MRI methods; 3) direct markers of other proteinopathies as they become available via PET, CSF and/or plasma; and 4) direct markers of neurodegeneration (N) including synaptic density, neuronal injury, atrophy patterns, and blood flow that are possible through PET, MRI, CSF, and/or blood modalities. We will closely collaborate with Cores B, C, D, E, F and H to conduct inclusive and broadly generalizable science by enrolling participants from underrepresented groups (URG) into the biomarker studies of the Wisconsin ADRC. Aim 1 focuses on obtaining and measuring relevant biomarkers from imaging and biofluids. In Aim 1a we collect the new mandated SCAN ATN PET imaging protocol on at least 24 ADRC participants per year and upload to NACC/SCAN. Aim 1b assays plasma samples from the clinical core and registry participants for ptau217, Aβ42/40, NfL and GFAP. Aim 1c will focus on CSF biomarker quantification. Aim 1d will focus on obtaining the ADRC standard MRI protocol on clinical core participants with a protocol features sequences for quantifying N, and aspects of V including ischemic lesions, perfusion, microhemorrhages, and vessel stiffness. Aim 2 will focus on biomarker interpretation including developing and applying appropriate thresholds for applicable biomarker modalities, which are needed to conduct the operations of the center and serve the needs of participants and investigators. Aim 3 will focus on providing infrastructure (such as image file management, image quality control, standard pipelines, and access to the fluid biomarker portfolio) and expertise to investigators for implementing appropriate biomarkers from our portfolio in research. Aim 4 will focus on sharing images and derived data with the local and natio...