<p>by Charles ffrench-Constant</p> The consequences of oligodendrocyte involvement in Alzheimer’s disease are poorly understood. Could a key role of gray-matter oligodendrocytes—activity-dependent adaptive myelination to sustain changes in activity—be perturbed, leading to cognitive loss? The consequences of oligodendrocyte involvement in Alzheimer’s disease are poorly understood. This Perspective suggests that activity-dependent adaptive myelination, a key role of grey-matter oligodendrocytes, could be perturbed, leading to cognitive loss.