Protein aggregation further disrupts synaptic architecture and memory functions in AD, a process exacerbated by a shift from the dynamic Hsp70/Hsp90 “chaperome” network to more rigid, maladaptive “epichaperomes.” Small-molecule inhibitors that disrupt the Hsp90–Hsp70 epichaperome, such as PU-H71 and PU-AD, have been shown to restore synaptic connectivity performance in the PS19 tauopathy model [113]. This evidence concerns the gene HSP90AB1 and Alzheimer disease.