HSP90B2P and Alzheimer disease: In summary, therefore, a primary failure in mechanisms regulating HSP could lead to chronically enhanced network activity in the initial stages of the disease, which in turn could drive compensatory synapse weakening and eventual elimination, together with the plasticity deficits (impaired LTP and facilitation of LTD) that are a key substrate of cognitive decline in the early stages of AD (Mucke and Selkoe, 2012; Styr and Slutsky, 2018; Figure 1).