Vardarajan BN, et al. - Aim of this study is to identify rare coding variants segregating with late-onset Alzheimer disease (LOAD) in Caribbean Hispanic families. In Caribbean Hispanic families with LOAD, whole-exome sequencing (WES) revealed ultra-rare missense mutations in Snf2-related CREBBP, activator protein (SRCAP), a gene expressed in the brain and mutated in Floating-Harbor syndrome. SRCAP was seen to be a potent coactivator of the CREB-binding protein and a regulator of DNA damage response involving ATP-dependent chromatin remodeling. The authors hypothesized that increased expression in LOAD suggested a compensatory mechanism altered in mutation carriers.