Myelin Damage and Its Role in Alzheimer’s Disease Pathology

Abstract: Recent research increasingly recognizes demyelination as a major contributor to the cognitive decline and neurodegeneration associated with Alzheimer’s disease. Myelin, a sheath that insulates axons and enables rapid signal conduction, is essential for neuronal communication. The degeneration of myelin, which slows neuronal signaling, results in poor learning, impaired memory, and reduced decision-making capacity. Despite the many detrimental effects of demyelination, the specific mechanisms responsible for myelin damage remain unclear. Understanding these mechanisms leading to Alzheimer’s disease is essential for developing effective treatment strategies to restore or preserve myelin integrity. Evidence from recent studies highlights promising approaches, including tissue-engineering methods like the use of hydrogel scaffolds and glial progenitor cell transplantation; neuromodulation approaches like neural stimulation and glutamate receptor modulation are also capable of fostering myelination. Additionally, there are also pharmacologic treatments like Lecanemab that may similarly support myelin preservation by reducing the processes culminating in myelin degradation. This review synthesizes findings from animal studies, human neuroimaging, and clinical trials to evaluate current and emerging approaches to maintaining and repairing myelin. These results stress the importance of integrating cellular, molecular, and bioengineering approaches to advance therapeutic development. Strengthening myelin-targeting strategies may support earlier diagnosis, more personalized treatment, and improved long-term outcomes for patients. By identifying these therapeutic directions, this review emphasizes the significance of targeting myelin repair to slow Alzheimer's disease progression and mitigate the cognitive and behavioral effects associated with the disorder.