PROJECT SUMMARY/ABSTRACT – CLINICAL CORE The Clinical Core (CC) of the Arizona ADRC is a consortium of five recruitment sites providing catchment areas throughout Phoenix and Tucson that comprise a standardized unit under a single Clinical Core Director. The CC has an overarching interest in the study of preclinical Alzheimer's disease (AD) and the accelerated evaluation of AD prevention therapies with emphasis on the development of blood-based biomarkers (BBBs). The CC will provide NACC-shared uniform data sets (UDS) and brain images and NCRAD-shared CSF, DNA and blood samples from about 1,650 well characterized longitudinally assessed research participants in our ADRC grant- supported Clinical Core, our organizationally and philanthropically supported Affiliated Brain and Body Donation Program (BBDP) and Affiliated APOE Program, and our pending NIA grant-supported APOE4/APOE2 Allelic Dose Cohort. Our Clinical Core will include 550 annually assessed dementia, mild cognitive impairment (MCI) and cognitively unimpaired participants, including about 300 who are enrolled our BBDP, about 200 from Arizona's underrepresented Hispanic/Latino and Native American communities, and those originally cognitively unimpaired participants in our Affiliated APOE Program and APOE4/APOE2 Allelic Dose Cohort after they progress to MCI and dementia. Our Affiliated BBDP will include about 500 additional participants in our BBDP with and without the clinical manifestations of AD, Parkinson's disease, and related dementias (ADRD), providing a combined resource of data and samples from about 800 BBDP participants, including about 100 BBDP participants per year who donate their brains and have comprehensive neuropathological assessments after they die. Our Affiliated APOE Program will include about 300 biennially assessed cognitively unimpaired APOE4 homozygotes, heterozygotes and non-carriers. Our pending APOE4/APOE2 Allelic Dose Grant will include about 300 biennially assessed age and APOE genotype-stratified participants with each of the six major APOE genotypes, including highest risk APOE4/4 and lowest risk APOE2/2 genotypes and those who remain cognitively unimpaired at older ages despite their genetic risk. The CC will provide an resource of annual NACC- and NCRAD-shared data and blood samples in BBDP participants to evaluate the accuracy of BBBs for AD/ADRD to support their neuropathological validation and use in research, drug development and clinical setting. It will provide a full set of NACC and NCRAD-shared clinical, Aβ PET, tau PET and MRI data and CSF, blood and DNA samples in 50 Hispanic/Latino, 50 Native American to help confirm the accuracy and support the use of BBBs in these understudied groups. It will provide additional NACC and NCRAD-shared data, biomarkers and samples in cognitively unimpaired participants at different levels of genetic and biomarker risk to support to support the use of BBBs and other measurements in the early detection and tracki...