Phosphatidylinositol binding clathrin assembly protein (PICALM or CALM), located on chromosome 11, may be a putative LOAD risk-factor gene. PICALM can play a role in APP endocytosis and Abeta generation. Additionally, its overexpression may increase Abeta cleavage and aggregation.157 Harold et al found strong association between two polymorphisms in PICALM and LOAD. Rs561655 is located within a transcription factor-binding site, and a silent mutation, rs592297, may be involved in the alternative splicing.158 Other SNPs in PICALM have also been suggested to be involved in LOAD, such as rs3851179 and rs541458.158
