The progression of Alzheimer’s disease is divided into stages based on the severity of behavioral and neural pathology (Braak & Braak, 1998; Palmer, 2002). AD-related neuropathies result in cell damage and death in a brain-regional progression moving from the entorhinal cortex to the hippocampus (HPC) and frontal cortex, and finally to limbic systems, including the AMY with corresponding escalation of behavioral pathology (Pietrzak et al., 2015; Sperling et al., 2011; Villemagne et al., 2013) (Fig. 2A). Cognitive decline is initially associated with Aβ and Tau pathology in the entorhinal cortex (mild). With disease progression, pathology spreads to the HPC and neocortex (moderate) and symptoms include more prominent memory loss. Finally, in the latter stages of AD, pathology progresses to the AMY and striatum (severe) with increasing pathology and severity of symptoms (Palmer et al., 2011) (Fig. 2A).
