Taken together, we hypothesize that the impotence of the LRP1-Aβ42 complex anchored in neuritic plaque to internalize is the causal cell mechanism resulting in neuronal cell membrane dysfunction that leads to the production of hyperphosphorylated tau protein, subsequent damage to intracellular transport pathways, and, finally, to the neuronal death seen in AD (see Figure 4a,b). This evidence concerns the gene LRP1 and Alzheimer disease.