Biomarkers.

Background: Individuals from diverse racial and ethnic groups are severely underrepresented in AD trials in part due to disproportionate biomarker ineligibility. Evidence from recent studies support plasma phosphorylated tau (P-tau217) as an early marker for brain Aβ pathology and a reliable marker in predicting elevated brain amyloid PET in cognitively unimpaired adults. We examined the relationship between P-tau217 and florbetapir PET standard uptake value ratios (SUVR) by self-reported racial and ethnic groups in preclinical AD studies.

Methods: We examined the relationship between baseline florbeptair PET SUVR and plasma P-tau217 levels (as determined by the electrochemiluminescence immunoassay), in cognitively unimpaired adults ages 65-85 with elevated amyloid PET (A4 Study, placebo arm, N=522) and participants who did not display elevated amyloid but were otherwise eligible for the A4 Study (LEARN, N=471). Given the small numbers across each subpopulation, participants were grouped into racial and ethnic underrepresented groups (RE-URG; N=100) and non-RE-URG (N=893), based on their self-identified race and ethnicity. A linear regression model was fit to determine differences in the relationship between plasma P-tau217 and florbetapir PET SUVR by RE-URG status, adjusting for age, and APOE ϵ4 carrier status.

Results: Demographic characteristics of RE-URG (N=100) and non-URG (N=893) are displayed in the Table. Groups were balanced across, age, sex, and education, with a higher proportion of APOE ℇ4 carriers among non-RE-URG (38.8%) vs RE-URG (24.0%). Mean plasma P-tau217 levels were the same across groups (Table). Results from the linear regression model suggest that the relationship between P-tau217 and florbetapir PET SUVR was similar across groups (p=0.22). Furthermore, APOE ℇ4 carrier status did not influence the relationship in either group (RE-URG p=0.61; non-RE-URG p=0.09).

Conclusion: These findings suggest that there is no difference in the relationship between plasma P-tau217 and elevated amyloid on florbetapir PET across racial and ethnic groups. Future analyses should corroborate these findings in a larger sample size, across different RE-URG sub-populations and examine whether plasma P-tau217 reflects the differential amyloid prevalence previously reported for other biomarkers of amyloid.

Acknowledgment: Lilly Clinical Diagnostics Laboratory for the performance of P-tau217 testing.