Myelin plays an essential role in brain structure and function and the human brain is uniquely dependent on the elaboration of this late evolutionary invention. Our brain has the most extensive and protracted process of myelination. The unique vulnerabilities of myelin and the oligodendrocytes that produce it are directly pertinent to many uniquely human neuropsychiatric diseases including many degenerative disorders such as AD, PD, and HD and the striking patterns of spread of their pathognomonic lesions across the brain in predictable symmetric bilateral patterns.
Age-related myelin breakdown releases considerable stores of iron and can promote tissue oxidative damage to which the brain is especially vulnerable. In brain, iron levels increase with age and are inexorably intertwined with the myelination and myelin breakdown processes. Increased iron levels may be directly toxic by promoting free radical reactions and indirectly contribute to pathologic changes through excitotoxicity or by promoting the development of proteinopathies (abnormal deposits of proteins) associated with several prevalent neurodegenerative diseases such as AD, PD, DLB, and possibly HD. Iron levels are abnormally elevated in these age-related degenerative brain diseases, suggesting that increased iron levels may contribute to the striking age-related manifestation of such diseases as well as influencing their age at onset and other phenotypic facets.
Magnetic resonance imaging technology permits the assessment of myelin breakdown as well as iron levels in vivo. There is close agreement between neuropsy-chological, neuropathologic, and imaging measures, suggesting that the process of myelin breakdown normally begins in early adulthood, accelerates as aging progresses, and underlies both age-related cognitive declines and the subsequent development of dementia-causing disorders. This myelin-centered model and the ability to measure the lifelong trajectory of myelin development, breakdown, and its impact on brain iron levels provides a framework for developing novel treatments as well as assessing the efficacy of currently available treatments.
Although many issues remain to be resolved regarding both normal aging and age-related disease states, the ability to track myelin breakdown and iron accumulation with MRI provides the opportunity to assess these processes directly in humans. MRI biomarkers can also provide a means to assess the efficacy of treatments aimed at mitigating myelin degeneration and iron toxicity in clinically healthy as well as symptomatic populations. Such treatments may have a wide spectrum of efficacy and potentially could delay or prevent brain aging and some of the uniquely human disorders associated with the aging process of the human brain.
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