Disease-Associated Oligodendrocyte: New Player in Alzheimer's Disease and CNS Pathologies

Abstract

Considerable evidence has shown that the breakdown of myelin has been linked to Alzheimer's disease (AD). Considering the vulnerability of oligodendrocytes to Alzheimer's disease, the myelin sheath breakdown and degeneration are easily induced, suggesting that dysfunction of the oligodendrocytes could be the first step in the progression at the early AD before the occurrence of amyloid and tau pathology. It is considered that amyloid β-peptide (Aβ)-mediated oligodendrocyte dysfunction and demyelination could be manifested through neuroinflammation, oxidative stress, and neuronal ferroptosis. With the development of single-cell sequencing technology, an oligodendrocyte state that increased in association with central nervous system brain pathology (designated as disease-associated oligodendrocytes) has been identified. In the current review, we examine the possible roles of oligodendrocytes in cognitive decline and their molecular characteristics in AD. Altogether, our findings elucidate that targeting oligodendrocytes may be a novel treatment or prevention option for AD.