The Interaction between Oligodendrocytes and Aβ in Alzheimer's Disease

Oligodendrocytes (OLs) are the primary myelinating cells in the central nervous system (CNS), responsible for maintaining the rapid conduction of nerve signals and ensuring neuronal stability through metabolic and nutritional support. Recent studies have reported that OLs are also involved in the development and progression of Alzheimer's disease (AD), particularly in the production and clearance of amyloid-beta (Aβ), exhibiting complex and critical regulatory functions. While traditional research has predominantly focused on the roles of neurons and microglia in Aβ metabolism, recent evidence indicates that OLs engage in a complex bidirectional interaction with Aβ in AD. On the one hand, OLs can produce Aβ, frequently generating aggregated and highly toxic Aβ42, which contributes to plaque expansion and disease progression. On the other hand, neuronderived Aβ exerts a concentration-dependent dual effect on OLs. At high concentrations, it induces oxidative stress and cell apoptosis, while at low concentrations, it promotes their differentiation and myelin repair functions. Therefore, OLs serve as both a "source" and a "target" of Aβ production and response, making them a key factor in AD pathogenesis. This review discusses the interaction between OLs and Aβ in AD, aiming to provide new perspectives on targeting OLs for AD therapy. Given the dual role of OLs in Aβ metabolism, targeting OLs dysfunction and the regulatory mechanisms underlying Aβ production and clearance could provide novel therapeutic strategies for AD. Future research should investigate the roles of specific OL populations (including oligodendrocyte precursor cells (OPCs), pre-myelinating OLs, and mature OLs) in Aβ generation and metabolism, focusing on the signaling pathways involved. Additionally, the molecular mechanisms by which OLs regulate other glial cells, such as astrocytes and microglia, through intercellular signaling to facilitate Aβ clearance and maintain neuroglial homeostasis warrant further exploration.