Recently it was found that another AD risk gene, PICALM, plays a central role in BBB transcytosis of Aβ, and it has been reported that extracellular binding of Aβ to Lrp1 induces an intracellular conformational change allowing for PICALM binding and endocytosis of the entire complex (Zhao et al., 2015). The gene discussed is PICALM; the disease is Alzheimer disease.