BDNF and Alzheimer disease: While the time frame for direct impact of Aβ in vitro on isolated, cultured neurons is greatly accelerated as compared with in vivo in AD pathology models or AD, the variation in local Aβ levels and other protective mechanisms (e.g., BDNF; Arancibia et al., 2008) act to prolong the time course for synaptotoxicity in vivo.