PET Core: Summary/Abstract The ADNI PET Core will continue its overall mission of standardizing PET data acquisition, performing quality control on all acquired data, preprocessing PET data to provide uniform resolution and formatting, and analyzing PET data to provide standard readouts that can be used by investigators around the world. Over time, the ADNI PET core has evolved to meet changing needs and the introduction of new technologies and the plans for ADNI4 represent another stage in this process. The crucial new features of the PET core will include the introduction of a new -amyloid PET tracer, [18F]NAV4694, so that ADNI4 will make use of 3 PET tracers as we continue use of [18F]Florbetaben and [18F]Florbetapir. We will also add 2 new tracers for monitoring deposition of pathological tau forms by adding [18F]MK6240 and [18F]PI2620 to the ongoing use of [18F]Flortaucipir, bringing tau PET tracers also to 3. As part of operations, we will harmonize all amyloid PET data to the centiloid scale, and develop methods for the harmonization of tau PET data. All continuing participants will remain on their existing tracers to ensure high quality longitudinal data, and new participants will be assigned to new tracers based on proximity to manufacturing sites. Another new feature of ADNI is the introduction of visual reads on all amyloid scans. These visual reads will be reported back to sites, where they can be returned to participants, and also can be used in analyses since visual reads have become an integral part of therapeutic trials. In addition, ADNI4 will complete the “early frames study” (by concluding enrollment and longitudinal scanning), acquiring dynamic PET data for the 20 min after injection to estimate perfusion effects and model regional cerebral blood flow as a potential neurodegeneration biomarker. The aims of the Core will be met by a strong administrative component with continuation of monthly meetings for optimal input into decision making, and by the data management and processing that includes image quality control and standardization performed at the University of Michigan and new quality control procedures for PET data analysis. All participants will undergo amyloid and tau PET imaging every 2 years, and individuals who are amyloid negative will continue to be followed so that we can examine “conversion” to amyloid positivity, and effects of high subthreshold and rising amyloid and tau levels in nominally negative individuals. The acquisition of high quality, longitudinal amyloid and tau data will be crucial to testing hypotheses concerning the validation of plasma -amyloid and tau measurements, cross-sectional and longitudinal relationships between biomarker and between biomarkers and cognition, and the examination of tau PET tracers as outcome measures in clinical trials.