Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2019 Biomarkers of insulin resistance, oxidative stress, and nutrition and the brain Kelsey Elizabeth McLimans Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Human and Clinical Nutrition Commons, Molecular Biology Commons, and the Neuroscience and Neurobiology Commons Recommended Citation McLimans, Kelsey Elizabeth, "Biomarkers of insulin resistance, oxidative stress, and nutrition and the brain" (2019). Graduate Theses and Dissertations. 17510. https://lib.dr.iastate.edu/etd/17510 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Biomarkers of insulin resistance, oxidative stress, and nutrition and the brain by Kelsey Elizabeth McLimans A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Nutritional Sciences Program of Study Committee: Auriel Willette, Major Professor John Crespi Anumantha Kanthasamy Lorraine Lanningham-Foster Matthew Rowling The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2019 Copyright © Kelsey McLimans, 2019. All rights reserved. ii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ............................................................................................................ v ABSTRACT ............................................................................................................................... vii CHAPTER 1. GENERAL INTRODUCTION .................................................................................... 1 Dissertation Organization .................................................................................................... 2 References ............................................................................................................................ 3 CHAPTER 2. LITERATURE REVIEW ............................................................................................ 5 Alzheimer’s Disease ............................................................................................................. 5 Obesity and Insulin Resistance ........................................................................................... 10 Reactive Oxygen Species .................................................................................................... 17 Vitamin B12 ........................................................................................................................ 21 References .......................................................................................................................... 27 CHAPTER 3. AUTOTAXIN IS RELATED TO METABOLIC DYSFUNCTION AND PREDICTS ALZHEIMER’S DISEASE OUTCOMES ........................................................................................ 41 Abstract .............................................................................................................................. 41 Introduction ....................................................................................................................... 42 Materials and Methods ...................................................................................................... 46 Results ................................................................................................................................ 51 Discussion ........................................................................................................................... 54 References .......................................................................................................................... 59 Tables and Figures .............................................................................................................. 65 CHAPTER 4. PERIPHERAL VERSUS CENTRAL INDEX OF METABOLIC DYSFUNCTION AND ASSOCIATIONS WITH CLINICAL AND PATHOLOGICAL OUTCOMES IN ALZHEIMER’S DISEASE .................................................................................................................................. 71 Abstract .............................................................................................................................. 72 Introduction ....................................................................................................................... 73 Materials and Methods ...................................................................................................... 75 Results ................................................................................................................................ 81 iii Discussion ........................................................................................................................... 84 Conclusion .......................................................................................................................... 88 References .......................................................................................................................... 90 Tables and Figures .............................................................................................................. 94 CHAPTER 5. IS CSF SOD1 A BIOMARKER OF TAU BUT NOT AMYLOID INDUCED NEURODEGENERATION IN ALZHEIMER’S DISEASE? ............................................................. 104 Abstract ............................................................................................................................ 104 Introduction ..................................................................................................................... 105 Innovation ........................................................................................................................ 106 Results .............................................................................................................................. 107 Discussion ......................................................................................................................... 110 Notes ................................................................................................................................ 113 References ........................................................................................................................ 118 Tables and Figures ............................................................................................................ 120 CHAPTER 6. SERUM VITAMIN B12, AND RELATED CUBILIN GENOTYPES, PREDICT NEURAL OUTCOMES ACROSS THE AD SPECTRUM ............................................................... 127 Abstract ............................................................................................................................ 127 Introduction ..................................................................................................................... 129 Methods ........................................................................................................................... 131 Results .............................................................................................................................. 136 Discussion ......................................................................................................................... 138 References ........................................................................................................................ 144 Tables and Figures ............................................................................................................ 149 CHAPTER 7. SERUM VITAMIN B12 IS RELATED TO IMPROVED EXECUTIVE FUNCTION IN YOUNG ADULTS .................................................................................................................... 157 Abstract ............................................................................................................................ 157 Introduction ..................................................................................................................... 158 Methods ........................................................................................................................... 160 Results .............................................................................................................................. 161 Discussion ......................................................................................................................... 162 Conclusion ........................................................................................................................ 163 iv References ........................................................................................................................ 164 Tables and Figures ............................................................................................................ 166 CHAPTER 8. GENERAL CONCLUSIONS .................................................................................