TITLE: NIH INCLUDE ACTC-DS – Bringing Advances in Tau PET imaging and blood- based biomarkers of Phospho-tau to the Trial-Ready Cohort – Down Syndrome (TRC-DS) ABSTRACT With this supplement, we request funding to implement multiple new assays to be performed on CSF and blood samples as well as the addition of Tau PET imaging on half of the participants in the Alzheimer's Clinical Trial Consortium – Down Syndrome (ACTC-DS) Trial Ready Cohort – Down syndrome (TRC-DS) Project. Tau PET is a critical biomarker in understanding AD pathology in DS and as in the sporadic population, seems to correlate more closely with cognitive decline. Moreover, recent findings indicate that Pospho-Tau-217 (Ptau217) may represent perhaps the most accurate CSF- and blood-based biomarker of AD and will thus be critically important to study in the DS population.