Our results provide the first evidence for the role of syndapin-2 in Aβ clearance from the brain through LRP1-mediated transcytosis across the brain endothelium, and that the process of healthy ageing also leads to a decline in the expression of syndapin-2, which is accelerated in Alzheimer’s disease. The gene discussed is LRP1; the disease is early-onset autosomal dominant Alzheimer disease.