Amyloid PET and Blood-Based Biomarkers of AD among Diverse Populations

PROJECT SUMMARY/ABSTRACT This application for a K23 career development award for Charles Windon, MD, will support his long-term goal of becoming an independent clinical researcher. Dr. Windon is a behavioral neurologist and Assistant Professor in the Department of Neurology at the University of California, San Francisco, within the Memory and Aging Center (UCSF MAC). He seeks to become an independent investigator in the field of biomarker- informed inequities research and address inequities in Alzheimer’s Disease and Related Dementias (AD/ADRD). The support provided by this K23 will allow Dr. Windon to achieve the following training goals (TG): TG1: knowledge in PET imaging analysis and plasma biomarker analysis; TG2: advanced statistical methodology knowledge for high complexity imaging and clinical data; TG3: skill building in analytic approaches to individual- and neighborhood-level SDOH; and TG4: grantsmanship, dissemination of clinical research, and other areas of professional development. He will incorporate the findings of his K23 into an R01 that develops and explores models validated in larger cohorts more richly characterized by SDOH measures and Alzheimer’s Disease and related dementias (AD/ADRD) biomarkers to best identify which pathological contributions to cognitive impairment should be emphasized in therapy for ethnoculturally diverse individuals. Dr. Gil Rabinovici, a world recognized leader in amyloid PET and fluid AD/ADRD biomarkers, will serve as primary mentor for this K23. He is joined by co-mentor Dr. Jacqueline Torres, a social epidemiologist who has extensive expertise in advanced epidemiologic and econometric methods to examine social determinants and inequities in AD/ADRD. Dr. Adam Boxer, an experienced researcher and clinical trials leader with expertise in blood-based biomarkers of AD/ADRD, Dr. Isabel Allen, an experienced professor with expertise in statistical analysis, and Dr. Amy Kind, a leading expert in neighborhood level social determinants, are collaborators. Dr. Windon will investigate in this proposal how global β-amyloid burden, measured by PET, and blood-based phosphorylated tau (p-tau) 217 and Neurofilament light (NfL) biomarkers are independently associated with AD/ADRD among diverse populations with varying social determinants of health (SDOH) profiles. Analysis of >2900 cognitively impaired diverse individuals with these biomarkers will be used for specific aims of: 1) Understanding differences in clinical presentation, dementia risk factors, SDOH profile, and rates of amyloid PET positivity between cognitively impaired Black/African American and Latinx individuals and Non-Latinx White individuals; 2) Understanding differences in β-amyloid burden by PET centiloid value between cognitively impaired Black/African American and Latinx and Non-Latinx White individuals and quantify relationships between p-tau 217 and NfL, respectively, and cognitive impairment among these groups; 3) Testing whether individual-level SDOH or neighborhood-level SDOH act as effect modifiers in the relationship between p-tau 217 and NfL and PET centiloid value, respectively, and cognition.