Fig. 1: Oligodendrocyte response at different stages of AD pathology.

a, Neuronal dysfunction and degeneration occurs with nonlinear kinetics. Initially, there is compensation and protection, but, as the pathology progresses, the dysfunction becomes increasingly evident. We hypothesize that neurodegeneration is slowed down by glial defense function. Once these protective mechanisms decline, neurodegeneration accelerates. b, Oligodendrocytes have an intimate anatomical and functional relationship with neurons. The diagram shows the relationship between oligodendrocytes and neurons at different stages of AD pathology. The normal function of oligodendrocytes is to support saltatory nerve conduction, to minimize neuronal energy consumption and to provide metabolic support. Once neurons become affected by increasing pathology, oligodendrocytes may transition into disease-associated states that provide immune modulatory function. The exhaustion of these functions may contribute to neurodegeneration.