MAPT and Alzheimer disease: PICALM also influences the pathways that directly contribute to the development of the pathological hallmarks of AD, including the accumulation of Aβ and hyperphosphorylated tau proteins in the brain (Xiao et al., 2012; Ando et al., 2013; Moreau et al., 2014; Xu et al., 2015; Zhao et al., 2015).