Myelin loss and
iron accumulation are cardinal features of aging and various
neurodegenerative diseases. Oligodendrocytes incorporate
iron as a metabolic substrate for myelin synthesis and maintenance. An emerging hypothesis in
Alzheimer's disease research suggests that myelin breakdown releases substantial stores of
iron that may accumulate, leading to further myelin breakdown and neurodegeneration. We assessed associations between
iron content and myelin content in critical brain regions using quantitative magnetic resonance imaging (MRI) on a cohort of cognitively unimpaired adults ranging in age from 21 to 94 years. We measured whole-brain myelin water fraction (MWF), a surrogate of myelin content, using multicomponent relaxometry, and whole-brain
iron content using susceptibility weighted imaging in all individuals. MWF was negatively associated with
iron content in most brain regions evaluated indicating that lower myelin content corresponds to higher
iron content. Moreover,
iron content was significantly higher with advanced age in most structures, with men exhibiting a trend towards higher
iron content as compared to women. Finally, relationship between MWF and age, in all brain regions investigated, suggests that brain myelination continues until middle age, followed by degeneration at older ages. This work establishes a foundation for further investigations of the etiology and sequelae of myelin breakdown and
iron accumulation in neurodegeneration and may lead to new imaging markers for
disease progression and treatment.