PSEN1 and Onset: In comparison with healthy controls and the early-onset AD group, the autosomal-dominant mutation carriers demonstrated focal volume loss in thalamic regions, which has recently been described as a potentially critical hub to explain the symptomology of the disease.21 Increased volume loss in this region has previously been reported in presymptomatic and symptomatic presenilin-1 mutation carriers compared with controls18 22 but not between presenilin-1 and sporadic early-onset AD as shown here.