It is possible that the presence of both SNPs in the 5′ region outside the gene may have an effect on the expression of PICALM. The gene product CALM co-localizes with amyloid precursor protein (APP) in vitro and in vivo, regulating APP internalization and subsequent Aβ generation, thus contributing to amyloid plaque load by its influence on Aβ metabolism (32, 33). The gene discussed is APP; the disease is amyloidosis.