Relationship between Plasma P-Tau217 and Amyloid PET in Racial and Ethnic Underrepresented Groups (RE-URG) Compared with Non RE-URG in LEARN and A4.

ABSTRACT

BACKGROUND: Individuals from diverse racial and ethnic groups are severely underrepresented in Alzheimer's disease trials in part due to disproportionate biomarker ineligibility. Evidence from recent studies support plasma phosphorylated tau 217 (P-tau217) as an early marker for brain Aß pathology and a reliable marker in predicting elevated brain amyloid PET in cognitively unimpaired adults. OBJECTIVES: To examine whether the relationship between P-tau217 and 18-F florbetapir PET standard uptake value ratios (SUVR) is influenced by race and ethnicity in the Anti-Amyloid treatment in Asymptomatic Alzheimer's disease (A4) preclinical AD studies. DESIGN: We conducted a retrospective analysis of A4 clinical trial and the LEARN natural history companion study data to evaluate the relationship between baseline P-tau217 and PET SUVR concentration levels by race and ethnicity. SETTING: The analysis was conducted on samples from participants enrolled across 65 study sites in the United States and Canada. PARTICIPANTS: Cognitively unimpaired adults aged 65-85 enrolled at North American sites in the A4 preclinical AD trial, pre-dose, (N=1018), and the LEARN (N=480) study. Participants were grouped into 2 categories, racial and ethnic underrepresented group (RE-URG) and non-RE-URG (nRE-URG) based on self-identification. MEASUREMENTS A mixed-effects regression model was fit to determine differences in the relationship between P-tau217 and PET SUVR by race and ethnicity, adjusting for age, and APOE ε4 carrier status. RESULTS: Results from the linear mixed-effects model support that there was no statistically significant effect of race and ethnicity on the relationship between P-tau217 and PET SUVR. CONCLUSION: These findings suggest that the relationship between plasma P-tau217 and PET SUVR is the same across race and ethnicity. Future analyses should corroborate these findings in a larger sample and examine whether plasma P-tau217 reflects the differential amyloid prevalence previously reported for other biomarkers of amyloid.