Another cause of the increased intracellular volume fraction could be the accumulation of glial cells observed in Alzheimer’s disease.48 Alternatively, as sodium channels are readily trafficked and recycled by the retromer complex, the decreased sodium signal could be driven by endosomal failure due to the decrease of SORL1 activity, leading to suboptimal cellular distribution of sodium channels.32,49 Based on our findings, we are, however, unable to anything but speculate on the exact mechanisms and their SORL1 dependency. The gene discussed is SORL1; the disease is early-onset autosomal dominant Alzheimer disease.