PICALM and Alzheimer disease: PICALM is downregulated in AD (Zhao et al., 2015); these reductions potentially contribute to an exacerbation in disease pathology by hindering LRP1-mediated Aβ transport, further tipping the Aβ balance in the brain (Figure 3D; Zlokovic et al., 2010; Sagare et al., 2012).