BIN1 and Alzheimer disease: Unlike the protective effect associated with a higher extracellular clusterin concentration (sCLU), iCLU is related to cell cytotoxicity, which may be involved in AD progression through interactions with tau and BIN1 [11,13]; that is, an rs7982G-dependent alternative splicing event may be implicated in AD by affecting the subcellular CLU localization, whose iCLU form is involved in AD progression generated via a partial loss (i.e., less intron retention) of the 5th exon.