In light of reported neuronal hyperexcitability in Alzheimer’s patients and models of Alzheimer’s disease [57,58], our work suggests that Aβ-HSPG interactions may affect the expression of HSPGs at the AIS, decreasing activation of CaMKII at the AIS and hence increasing neuronal excitability. This evidence concerns the gene HSPG2 and early-onset autosomal dominant Alzheimer disease.