Given the many AD risk genes associated with endocytosis86-91 (e.g. PICALM, SORL1, CD2AP, BIN1), as well as previous reports of age-related decline in CME-associated genetic signatures in the human brain borders92, we believe further interrogation of the role of endocytosis by brain border immune cells will deepen our understanding of AD pathogenesis with the potential of uncovering new therapeutic targets. The gene discussed is PICALM; the disease is Alzheimer disease.