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

Abstract

Introduction: Alzheimer'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.

Methods: We 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 (Aβ)40, Aβ42, Aβ42/Aβ40, 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.

Results: Greater impairment, older age, and carrying an apolipoprotein E (apoE) ε4 allele were associated with greater amyloid burden. Areas under the receiver operating characteristic curve for amyloid status of plasma Aβ42/Aβ40, p-tau181, and p-tau217 with amyloid positivity were ≥ 0.7117 for all ethnoracial groups (p-tau217, ≥0.8128). Age and apoE ε4 adjustments and imputation of biomarker values outside limit of quantitation provided small improvement in predictive power.

Discussion: Blood-based biomarkers are highly associated with amyloid PET/CSF results in diverse populations enrolled at clinical trial sites.

Highlights: Amyloid beta (Aβ)42/Aβ40, 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.

Keywords: Alzheimer's disease; Alzheimer's disease blood‐based biomarkers; Alzheimer's disease ethnic and racial differences; Bio‐Hermes Study; amyloid beta 40; amyloid beta 42; amyloid beta 42/40; clinical trials; phosphorylated tau181; phosphorylated tau217; screening.

FIGURE 1

Bio‐Hermes Study CONSORT diagram. AD, Alzheimer's disease; CONSORT, Consolidated Standards of Reporting Trials; CSF, cerebrospinal fluid; PET, positron emission tomography; URP, underrepresented populations.

FIGURE 2

ROC curves for prediction of brain PET or CSF amyloid positivity adjusted for age and apoE ε4 status with imputed values. Aβ, amyloid beta; apoE, apolipoprotein E; CSF, cerebrospinal fluid; PET, positron emission tomography; p‐tau, phosphorylated tau; ROC, receiver operating characteristic.