PROJECT SUMMARY- BIOMARKER CORE (CORE G) The Biomarker Core (BMC) of the Wisconsin Alzheimer's Disease Research Center (ADRC) represents the capability and infrastructure for peering into the brain in vivo to obtain biological markers of Alzheimer's disease (AD) and related disorders and non-disease-specific qualities characterizing brain health and resilience. Since the pre-clinical time frame of AD is a major emphasis of the ADRC, and since it is increasingly understood that AD pathology occurs well before its symptoms, the charge of this core is to provide the necessary capabilities, tools, and infrastructure to investigators to characterize as accurately as possible the early in-vivo changes of AD, effect of risk and resilience factors, and effect of prevention strategies on relevant biomarkers. The core will focus on collecting, quality checking, and curating several types of AD-relevant biomarkers including a) markers indicative of AD - defined by amyloid plaques and neurofibrillary tangles, and ascertainable by molecular PET imaging or cerebrospinal fluid (CSF) assays; b) markers of cerebrovascular diseases - the second most common etiology (or etiologies) of cognitive decline and ascertainable by new MRI methods; c) markers of other neurodegenerative diseases as they become available via CSF or PET; and d) markers of general brain health including synaptic density, neuronal injury, atrophy, connectivity, inflammation, and blood flow that are possible through PET, MRI and CSF modalities. To meet these goals, we will accomplish the following aims: Aim 1: Obtain biological markers of AD's hallmark neuropathological features - amyloid plaques and neurofibrillary tangles with CSF and/or molecular PET imaging. Aim 2: Collect biomarkers of concomitant features, such as vascular disease, inflammation, and neuronal death. Aim 3: Develop method for interpreting biomarker readouts, particularly for Amyloid (A), tau (T) and neurodegeneration (N). Aim 4: Support ADRC investigators with infrastructure and analytic support. Aim 5: Share images, fluid, and derived data with the National Alzheimer's Coordinating Center (NACC), local investigators, and other qualified investigators throughout the world. Aim 6: Expand the Center's biomarker capability, including a) adopting new methods and modalities in this fast-changing field, and b) for harmonizing previously collected data or multi-site data with current or future collection methods. The BMC will work interactively with the other ADRC cores to serve the needs of the ADRC investigators as efficiently as possible and deliver high quality data to NACC and other users so we, as a field, can come to answers faster in detecting and intervening effectively in AD.