Myelin Pathology in Alzheimer's Disease: Potential Therapeutic Opportunities

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and cognitive decline. Despite significant efforts over several decades, our understanding of the pathophysiology of this disease is still incomplete. Myelin is a multi-layered membrane structure ensheathing neuronal axons, which is essential for the fast and effective propagation of action potentials along the axons. Recent studies highlight the critical involvement of myelin in memory consolidation and reveal its vulnerability in various pathological conditions. Notably, apart from the classic amyloid hypothesis, myelin degeneration has been proposed as another critical pathophysiological feature of AD, which could occur prior to the development of amyloid pathology. Here, we review recent works supporting the critical role of myelin in cognition and myelin pathology during AD progression, with a focus on the mechanisms underlying myelin degeneration in AD. We also discuss the complex intersections between myelin pathology and typical AD pathophysiology, as well as the therapeutic potential of pro-myelinating approaches for this disease. Overall, these findings implicate myelin degeneration as a critical contributor to AD-related cognitive deficits and support targeting myelin repair as a promising therapeutic strategy for AD.