Salivary Lactoferrin as a Robust Biomarker of Alzheimer’s Disease Open Access

Abstract

Background: Pathological changes linked to Alzheimer’s Disease (AD) emerge years before the behavioral symptoms do. Thus, research has focused on developing accessible biomarkers that can accurately differentiate individuals who are likely to develop AD and reliably measure signs of disease progression. Lactoferrin (Lf) is an iron-binding antimicrobial glycoprotein found in all biological fluids, and its concentration in saliva has been correlated with AD signs. Previous studies have found mixed results, so this pilot project aims to determine if the investigation of salivary lactoferrin (sLF) as a biomarker for AD is worth continuing. Moreover, understanding the variability of sLF across races is imperative to assess its clinical usefulness.

Methods: Participants were middle to older-aged African American (AA) and white individuals at risk for AD due to parental history of the disease. We collected saliva samples after an 8 hour fast, and administered a cognitive battery to assess executive function, memory, visuospatial ability, attention, and verbal fluency. We examined the relationship between sLF concentration and cognitive performance. We also examined differences in sLF levels across races.

Results: We enrolled 17 middle to older-aged (age = 60.29 ± 9.7 years) subjects. There was a 50- 50 split between AA and whites. After controlling for age, sex, race, and years of education, we found a significant correlation between sLF and Digit Span Memory Test (DSMT) scores (P = 0.013). Furthermore, we found a correlation that is approaching significance between sLF and Mental Rotation Test scores (P = 0.194). Finally, we found no significant difference in average sLF concentration across AA and whites.

Conclusions: A decline in visuospatial ability and memory concerns are some of the earliest signs of cognitive deterioration in AD patients. Thus, we believe that the positive correlation found between sLF and measures of cognitive performance warrants more studies following sLF as a possible early biomarker for AD. Furthermore, the similarity in sLF concentration between AA and whites suggest a potential use as a biomarker in individuals regardless of their race. More studies measuring the relationship between sLF and other hallmark AD biomarkers, following healthy subjects longitudinally, and measuring differences across other races are needed to assess its clinical usefulness as a robust biomarker for AD. 

Table of Contents

Table of Contents

1. Introduction..........................................................................................9

1.1 Alzheimer’s Disease..............................................................................9

1.2 Salivary Biomarkers.............................................................................10

1.3 Salivary Lactoferrin.............................................................................11

1.4 Animals Models.................................................................................12

1.5 Clinical and Translational Studies in Humans..............................................14

1.6 Rationale.........................................................................................16

2. Materials and Methods...........................................................................18

2.1 Ethics..............................................................................................18

2.2 Subjects...........................................................................................19

2.3 Sample Collection, Processing, and Protein Quantification...............................20

2.4 Neuropsychological Assessment..............................................................21

2.5 Statistical Analyses..............................................................................21

3. Results ................................................................................................22

3.1 Demographics, Cognitive and sLF Measures ................................................22

3.2 Correlation Between Salivary Lactoferrin and Memory...................................23

3.3 Correlation Between Salivary Lactoferrin and Spatial Cognition.........................24

3.4 Difference in Salivary Lactoferrin Levels Across Races ...................................25

4. Discussion............................................................................................26

5. References............................................................................................30 

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	Salivary lactoferrin Alzheimer's disease Neuroscience Biomarker
Committee Chair / Thesis Advisor	Wharton, Whitney , Emory University
Committee Members	Roesch, Leah, Emory University Hue, Gillian , Emory University

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