Why Inclusion Matters for Alzheimer's Disease Biomarker Discovery in Plasma

J Alzheimers Dis. 2021;79(3):1327-1344. doi: 10.3233/JAD-201318.

Abstract

Background: African American/Black adults have a disproportionate incidence of Alzheimer's disease (AD) and are underrepresented in biomarker discovery efforts.

Objective: This study aimed to identify potential diagnostic biomarkers for AD using a combination of proteomics and machine learning approaches in a cohort that included African American/Black adults.

Methods: We conducted a discovery-based plasma proteomics study on plasma samples (N = 113) obtained from clinically diagnosed AD and cognitively normal adults that were self-reported African American/Black or non-Hispanic White. Sets of differentially-expressed proteins were then classified using a support vector machine (SVM) to identify biomarker candidates.

Results: In total, 740 proteins were identified of which, 25 differentially-expressed proteins in AD came from comparisons within a single racial and ethnic background group. Six proteins were differentially-expressed in AD regardless of racial and ethnic background. Supervised classification by SVM yielded an area under the curve (AUC) of 0.91 and accuracy of 86%for differentiating AD in samples from non-Hispanic White adults when trained with differentially-expressed proteins unique to that group. However, the same model yielded an AUC of 0.49 and accuracy of 47%for differentiating AD in samples from African American/Black adults. Other covariates such as age, APOE4 status, sex, and years of education were found to improve the model mostly in the samples from non-Hispanic White adults for classifying AD.

Conclusion: These results demonstrate the importance of study designs in AD biomarker discovery, which must include diverse racial and ethnic groups such as African American/Black adults to develop effective biomarkers.

Keywords: African American; Alzheimer’s disease; Black; biomarker; discovery; disparities; machine learning; plasma; proteomics; race.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / statistics & numerical data*
  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Machine Learning
  • Male
  • Patient Selection
  • Proteomics
  • Support Vector Machine
  • Whites / statistics & numerical data

Substances

  • Biomarkers