Demyelination within brain white matter is often observed in late life and is typically exacerbated in Alzheimer’s disease (AD). Indeed, prior studies have linked reduced white matter myelin content with aging, cognitive impairment, genetic risk factors of AD, and biomarkers of AD pathology and neurodegeneration. Interestingly, observations of post-mortem brains inflicted with AD pathology have noted that the development of such pathology inversely mirrors cortical myelogenesis. However, few studies to date have investigated the trajectories of cortical myelin in late life, and studies assessing relationships with AD pathology have led to confounding results. Here, through the use of high fidelity quantitative relaxometry (R1) mapping, a metric sensitive to brain myelin content, this dissertation includes three specific aims that expand upon our understanding of the role of cortex-specific myelin in healthy and diseased aging. The first aim examines age-related relaxometry changes in the cortex, as well as associations with performance on cognitive tests and cortical alterations in individuals presenting with Alzheimer’s clinical syndrome. The second aim assesses the effects of genetic risk factors including sex and apolipoprotein E genotype on cortical myelin. Finally, through the use of cerebrospinal fluid (CSF) biomarkers obtained via lumbar puncture in addition to imaging markers derived from amyloid and tau positron emission tomography (PET) imaging, the third aim identifies relationships between CSF biomarkers of AD pathology and neurodegeneration, as well as confirms the inverse spatial distributions of cortical myelin and AD pathology in vivo. Importantly, throughout this dissertation, all observations made within the cortex are reported in direct comparison to myelin content in adjacent white matter. This work adds to the growing body of literature aimed and elucidating the role of myelin in aging and AD-related pathogenesis and progression.