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.
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This post is Copyright: Richard C. Mohs,
Douglas Beauregard,
John Dwyer,
Jennifer Gaudioso,
Jason Bork,
Tamiko MaGee‐Rodgers,
Mickeal N. Key,
Diana R. Kerwin,
Lynn Hughes,
Cyndy B. Cordell,
The Bio‐Hermes Collaborative Group,
Jessie Nicodemus‐Johnson,
Craig Mallinckrodt,
Robin Wolz,
Kevin Yarasheski,
Joel B. Braunstein,
Tim West,
Philip Verghese,
Kris Kirmess,
Matthew Meyer,
David Wilson | February 28, 2024