Work

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

Year: 2021

Type: article

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.

Source: Journal of Alzheimer s Disease

DOI: 10.3233/jad-201318

Authors: Mostafa J. Khan, Heather Desaire, Oscar L. Lopez, M. Ilyas Kamboh, Renã A.S. Robinson

Institutions: Vanderbilt University, University of Kansas, University of Pittsburgh, Vanderbilt University Medical Center

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDGs: Good health and well-being, Reduced inequalities

Open Access status: green

Funders: National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development