HABS-HD - Project 1

HABS-HD PROJECT 1 ABSTRACT The 2018 AT(N) framework provided the field with the first biological conceptualization of Alzheimer’s disease (AD) for the explicit purpose of advancing clinical trials. In fact, the first amyloid-lowering drug (aducanumab) recently received FDA approval. However, nearly all data supporting the framework itself, as well as the clinical trials, comes from clinic-based research among non-Hispanic white (NHW) individuals. By 2060, the U.S. will become largely “non-white” with 15% of the population being African American (AA) and 27.5% being Hispanic (65% of which are Mexican American [MA]). AAs currently have the highest burden of AD and AD related dementias (ADRD) while Hispanics will experience the greatest increase in AD/ADRDs by 2060. Therefore, there is an urgent need to understand the relevance of the AT(N) framework, and associated biomarker-based therapeutics, for 43% of the U.S. population. Additionally, while there is a wealth of literature demonstrating that factors in early adulthood have a significant impact on late-life dementia risk, our understanding of the impact of these factors on the earliest signs and progression patterns of the fundamental biomarkers of AD among diverse communities remains largely unknown. The Health & Aging Brain Study – Health Disparities (HABS-HD) is the first large-scale, community-based project to simultaneously study each of the AT(N) defined biomarkers across adulthood among the three most prevalent racial/ethnic groups in the U.S., AAs, MAs and NHWs. The long-term goal of HABS-HD is to establish population-specific informed precision medicine for novel AD treatment and prevention strategies in line with NIA AD+ADRD Milestone 1. Project 1 will test the hypothesis that the timing, sequence, trajectories, progression and cognitive impact of the AT(N) biomarkers differ among African Americans, Mexican Americans, and non-Hispanic whites. Aim 1: Examine the longitudinal sequence, trajectories, progression and cognitive impact of AT(N) defined biomarkers among African Americans, Mexican Americans, and non-Hispanic whites. Aim 2: Examine the utility of blood- based biomarker profiles for screening for subsequent PET and/or MRI-based AT(N) confirmatory diagnostic methods among Mexican Americans, African Americans, and non-Hispanic whites. Aim 3: Examine the impact of genomic markers on AT(N) defined biomarkers among African Americans, Mexican Americans and non- Hispanic whites. Aim 4: Collaborate with Projects 2 and 3 to develop a comprehensive understanding of the impact of diverse biological, exposome, and sociocultural factors on AT(N) defined biomarkers across diverse populations. Exploratory Aim 5: Compare AT(N) biomarker data from HABS-HD with that from other large- scale initiatives such as ADNI, LEADS, ADCs, WHICAP, SOL/INCA, ABC-DS, New IDEAS and others.