Telomeres and the brain an investigation into the relationships of leukocyte telomere length with functional and structural attributes of the brain

.................................................................................................................................... 2 Populärvetenskaplig sammanfattning .............................................................................. 4 List of commonly used abbreviations ............................................................................... 6 Original Papers ........................................................................................................................ 7 Introduction ............................................................................................................................. 9 The beginning of the end ...................................................................................................... 9 The telomere ....................................................................................................................... 10 Telomere functions and telomere length shortening .......................................................... 11 Telomere lengthening ......................................................................................................... 12 Telomere length, disease, and aging .................................................................................. 13 Telomeres and psychiatry ................................................................................................... 17 Telomere length in the brain .............................................................................................. 18 The aging brain ................................................................................................................... 19 The HPA axis ....................................................................................................................... 21 Apolipoprotein E ................................................................................................................. 24 Aims .......................................................................................................................................... 26 General aim ......................................................................................................................... 26 Specific aims ....................................................................................................................... 26 Materials and Methods........................................................................................................ 27 Study participants ............................................................................................................... 27 The Betula Study .......................................................................................................... 27 The UmeDep sample .................................................................................................... 27 Telomere length measurements ......................................................................................... 29 Apolipoprotein E genotyping .............................................................................................. 30 Dexamethasone suppression test ....................................................................................... 31 Additional laboratory procedures....................................................................................... 31 Magnetic resonance imaging .............................................................................................. 32 Hippocampal volume ................................................................................................... 32 Brain atrophy and white matter hyperintensities ....................................................... 32 Cognitive assessments ........................................................................................................ 33 Questionnaires .................................................................................................................... 34 Ethics ................................................................................................................................... 35 Statistical methods .............................................................................................................. 35 Results and Discussion ....................................................................................................... 37 Telomeres and apoliprotein E ............................................................................................ 37 Telomeres and cognition .................................................................................................... 39 Telomeres and structural measures of the brain ............................................................... 41 The hippocampus ......................................................................................................... 41 Brain atrophy and white matter hyperintensities ....................................................... 43 Telomeres and depression .................................................................................................. 44 Telomeres and the HPA axis ............................................................................................... 45 Methodological issues ......................................................................................................... 48 Telomere length measurement .................................................................................... 48 Leukocyte subsets ......................................................................................................... 49 Limitations ................................................................................................................... 49 Study samples ............................................................................................................... 49 Concluding Remarks............................................................................................................ 51 Acknowledgements .............................................................................................................. 54 References .............................................................................................................................. 55