While theoretically appealing, the peripheral sink hypothesis seems unlikely to operate for Aβ aggregates in Alzheimer's disease (Georgievska et al, 2015; Honig et al, 2018), but it will be interesting to learn whether it may be a contender to explain the reduction of Notch3 ECD aggregates following active immunization. The gene discussed is NOTCH3; the disease is early-onset autosomal dominant Alzheimer disease.