The Bio-Hermes Study: Biomarker database developed to investigate blood-based and digital biomarkers in community-based, diverse populations clinically screened for Alzheimer's disease

INTRODUCTIONAlzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many are not amyloid positive. Use of blood-based biomarkers may reduce screen failures.METHODSWe recruited 755 non-Hispanic White, 115 Hispanic, 112 non-Hispanic Black, and 19 other minority participants across groups of cognitively normal (n = 417), mild cognitive impairment (n = 312), or mild AD (n = 272) participants. Plasma amyloid beta (A beta)40, A beta 42, A beta 42/A beta 40, total tau, phosphorylated tau (p-tau)181, and p-tau217 were measured; amyloid PET/CSF (n = 956) determined amyloid positivity. Clinical, blood biomarker, and ethnicity/race differences associated with amyloid status were evaluated.RESULTSGreater impairment, older age, and carrying an apolipoprotein E (apoE) epsilon 4 allele were associated with greater amyloid burden. Areas under the receiver operating characteristic curve for amyloid status of plasma A beta 42/A beta 40, p-tau181, and p-tau217 with amyloid positivity were >= 0.7117 for all ethnoracial groups (p-tau217, >= 0.8128). Age and apoE epsilon 4 adjustments and imputation of biomarker values outside limit of quantitation provided small improvement in predictive power.DISCUSSIONBlood-based biomarkers are highly associated with amyloid PET/CSF results in diverse populations enrolled at clinical trial sites.Highlights Amyloid beta (A beta)42/A beta 40, phosphorylated tau (p-tau)181, and p-tau 217 blood-based biomarkers predicted brain amyloid positivity. P-tau 217 was the strongest predictor of brain amyloid positivity. Biomarkers from diverse ethnic, racial, and clinical cohorts predicted brain amyloid positivity. Community-based populations have similar Alzheimer's disease (AD) biomarker levels as other populations. A prescreen process with blood-based assays may reduce the number of AD trial screen failures.