Predicting amyloid PET positivity using plasma p-tau181 and other blood-based biomarkers

Hyuk Sung Kwon, Eun Hye Lee, Hyung Ji Kim, So Hee Park, Hyun Hee Park, Jee Hyang Jeong, Seong Ho Koh, Seong Hye Choi, Jae Hong Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: This study aimed to determine the efficacy of combining plasma phosphorylated tau (p-tau)181, amyloid beta (Aβ)42/Aβ40, neurofilament light (NfL), and apolipoprotein E (APOE) genotypes for detecting positive amyloid positron emission tomography (PET), which is little known in the Asian population, in two independent cohorts. Methods: Biomarkers were measured using a single-molecule array (Simoa) in a cohort study (Asan). All participants underwent amyloid PET. Significant changes in the area under the curve (AUC) and Akaike Information Criterion values were considered to determine the best model. The generalizability of this model was tested using another cohort (KBASE-V). Results: In the Asan cohort, after adjusting for age and sex, p-tau181 (AUC = 0.854) or APOE ε4 status (AUC = 0.769) distinguished Aβ status with high accuracy. Combining them or adding NfL and Aβ42/40 improved model fitness. The best-fit model included the plasma p-tau181, APOE ε4, NfL and Aβ42/40. The models established from the Asan cohort were tested in the KBASE-V cohort. Additionally, in the KBASE-V cohort, these three biomarker models had similar AUC in cognitively unimpaired (AUC = 0.768) and mild cognitive impairment (MCI) (AUC = 0.997) participants. Conclusions: Plasma p-tau181 showed a high performance in determining Aβ-PET positivity. Adding plasma NfL and APOE ε4 status improved the model fit without significant improvement in AUC.

Original languageEnglish
Article numbere12502
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume15
Issue number4
DOIs
StatePublished - 1 Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.

Keywords

  • APOE
  • Alzheimer's disease
  • amyloid beta
  • amyloid positron emission tomography
  • neurofilament light
  • p-tau181

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