MAPT and Alzheimer disease: Several lines of evidence from in vitro and in vivo animal studies implicate astrocytes early in AD pathogenesis via several mechanisms [94], including increased Aβ synthesis and release, neuronal and astrocytic tau aggregation, neuroinflammation, increased oxidative stress, glutamate excitotoxicity due to disrupted astrocyte–neuron signaling, and impaired energy metabolism, which ultimately lead to neuronal and synaptic dysfunction.