FBM Core Summary/Abstract Recent advances in ultrasensitive blood biomarker assays for Alzheimer’s disease (AD) pathophysiology suggest that plasma biomarkers can revolutionize AD research and clinical practice. The Fluid Biomarker and Methodology (FBM) Core was created in PPG4 in response to these advances and will be responsible for coordinating blood collections, pre-analytical procedures, banking, analysis, and supplying continuous blood biomarker values to the projects. The FBM Core will generate results for all projects and will be integrated with all other cores. We will provide quality-controlled results of blood biomarkers in a format that can be easily used by projects for the analyzes associated with their aims. In collaboration with the neuroimaging and neuropathology teams, we will contribute to the validation of plasma biomarker assays previously developed by FBM Core team members and other groups against better-validated neuroimaging and postmortem outcomes. The FBM Core will seek to collaborate with several large-scale multi-site studies in the field of AD and related dementia to advance the knowledge of blood biomarkers using a big data approach. We will hold monthly meetings with other PPG researchers to discuss blood collection and analysis, as well as to discuss methodological and scientific aspects of blood biomarkers. The FBM Core will also provide training for students, postdocs, and faculty in fluid biomarker methods and analyses. It is important to emphasize that the optimization of neuroimaging biomarker techniques in the previous PPG cycles has placed the FBM Core in a privileged position to use these state-of-art neuroimaging outcomes to support the measures obtained with the new blood biomarker assays. The specific aims of the FBM Core are: (Aim 1) To coordinate the collection, pre-analytical procedures, storage, and analysis of blood plasma biomarkers across the PPG4. (Aim 2) To provide quality- controlled plasma biomarker values of Aβ, tau, neurodegeneration, and neuroinflammation in support of the aims described in detail in Projects 1-4. (Aim 3) In collaboration with the Imaging Biomarkers Methodology Core, we aim to validate plasma biomarker assays against neuroimaging outcomes. (Aim 4) In collaboration with the neuropathology team (Project 4), we aim to validate plasma biomarker assays against postmortem pathological outcomes. (Aim 5) To train students, post-doctoral fellows, and faculty in plasma biomarker methods. In the present study, we will generate the first large-scale longitudinal dataset with blood and neuroimaging measures of astrogliosis, Aβ, tau, and neurodegeneration. The results generated by the projects with the data provided by the FBM Core will help to elucidate the complex interactions between multiple pathologies in AD. The validation of blood biomarker measurements against better-established neuroimaging and postmortem outcomes will indicate the advantages and caveats of using these plasma bi...