Racial Differences in Salivary Biomarkers and Cognitive Function: Assessing Alzheimer’s Risk in Underrepresented Populations Restricted; Files Only

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which early detection remains a critical challenge. Current biomarker approaches often rely on cerebrospinal fluid or neuroimaging methods that are invasive, costly, and difficult to implement in large or diverse populations. Saliva is an emerging, non-invasive biofluid of interest for detecting AD-related biomarkers; however, its clinical utility remains under investigation, with ongoing efforts focused on determining whether salivary biomarkers reliably reflect those observed in cerebrospinal fluid (CSF) and blood. Limited research has examined salivary biomarkers in racially diverse populations or explored their relationships with cognitive performance. 

This study examined associations between salivary biomarkers and cognitive performance in a community-based sample of adults aged 30-80 (N=73). Specifically, we aimed to assess relationships between salivary AD-related biomarkers and cognitive function, determine whether biomarker levels differ by race, and evaluate whether biomarker-cognition relationships vary across racial groups. Participants provided saliva samples and completed a comprehensive cognitive battery assessing global cognition, executive function, memory, and visuospatial ability. Salivary concentrations of amyloid-B42 (AB42), total tau (t-tau), phosphorylated tau (p-tau181), lactoferrin, and alpha-synuclein were measured using enzyme-linked immunosorbent assays (ELISA). 

Black participants demonstrated significantly lower salivary concentrations of p-tau181, t-tau, and alpha-synuclein compared with Non-Hispanic White (NHW) participants, despite showing lower cognitive performance across several domains. No racial differences were observed for lactoferrin or AB42. Several biomarkers showed modest associations with cognitive outcomes.

These findings suggest that salivary biomarkers may reflect differential patterns across racial groups and support their continued investigation as a non-invasive approach for AD research. Importantly, this work highlights the need for further validation of biomarkers in diverse populations to ensure equitable and accurate detection and treatment across groups.

Table of Contents

Abstract .................................................................................................................................................................................................................................................................... i

Acknowledgements .................................................................................................................................................................................................................................................. iv

Table of Contents ...................................................................................................................................................................................................................................................... v

List of Tables .......................................................................................................................................................................................................................................................... vii

List of Figures ........................................................................................................................................................................................................................................................ viii

1. Introduction ............................................................................................................................................................................................................................................................. 1

2. Methods .................................................................................................................................................................................................................................................................... 7

2.1 Participant Recruitment and Study Populations

2.2 Demographics and Implications for Biomarker Focus

2.3 Saliva Collection Protocol

2.4 Saliva Analysis Protocol

2.5 Cognitive Testing

2.5a Administration

2.5b Cognitive Domains, Tests, and Reliability

2.6 Statistical Analyses

3. Results .................................................................................................................................................................................................................................................................... 13

3.1 Participant Characteristics

3.2 Salivary Biomarker Descriptive Statistics and Racial Differences

3.3 Racial Differences in Cognitive Performance

3.4 Associations Between Salivary Biomarkers and Cognitive Performance

3.5 Sex Differences

3.6 Summary of Results

4. Discussion ............................................................................................................................................................................................................................................................... 22

4.1 Overview of Key Findings

4.2 Racial Differences in Salivary Alzheimer’s Disease Biomarkers

4.3 Racial Differences in Cognitive Performance

4.4 Associations Between Salivary Biomarkers and Cognitive Function

4.5 Implications for Saliva as a Non-Invasive Biomarker

4.6 Implications for Future Care

4.7 Strengths and Limitations

4.8 Future Directions

5. Conclusions ............................................................................................................................................................................................................................................................ 32

6. References .............................................................................................................................................................................................................................................................. 34

7. Appendix ................................................................................................................................................................................................................................................................. 41

7.1 Previous Study on Serum Biomarkers

7.2 Expanding the Study: Saliva-Based Approach and Increased Inclusivity

7.3 Implications for Personalized Medicine

List of Tables

Table 1. Participant Characteristics by Race. …………………………………………………………………………………………………………………………………………………………………………………… 15

Table 2. Salivary Biomarker Levels by Race. ……………………………………………………………………………………………………………………………………………………………………………………… 16

Table 3. Cognitive Performance by Race. ………………………………………………………………………………………………………………………………………………………………………………………… 18

Table 4. Correlations Between Salivary Biomarkers and Cognitive Measures. …………………………………………………………………………………………………………………………………………… 20

Supplementary Table 1. Pearson correlations between salivary biomarkers and cognitive measures across the full sample. ………………………………………………………………………………… 44

Supplementary Table 2. Salivary AD-related biomarkers by sex. …………………………………………………………………………………………………………………………………………………………… 45

List of Figures

Figure 1. Racial differences in salivary AD-related biomarkers. ……………………………………………………………………………………………………………………………………………………………… 17

Figure 2. Racial differences across cognitive domains. ………………………………………………………………………………………………………………………………………………………………………… 19

Figure 3. Associations between salivary biomarkers and cognitive performance. ……………………………………………………………………………………………………………………………………… 21

Figure 4. Heatmap of associations between salivary biomarkers and cognitive domains. …………………………………………………………………………………………………………………………… 22 Supplementary Figure 1. ELISA Standard Curves for Salivary Biomarkers. ……………………………………………………………………………………………………………………………………………… 46

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Aging Biology, Neuroscience
Keyword	non-invasive diagnostics diagnostic thresholds cognitive function Alzheimer’s disease health disparities alpha-synuclein t-tau salivary biomarkers population differences p-tau181
Committee Chair / Thesis Advisor	Butts, Brittany, Emory University
Committee Members	Wharton, Whitney, Emory University Nam, Edward, Emory University

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