In support of the first hypothesis, up-regulation of amyloid precursor protein (APP) and/or β-site APP cleaving enzyme 1 (BACE1) has been observed in reactive astrocytes (GFAP+) in 5XFAD and Tg2576 transgenic mice [54,55], as well as in human AD hippocampus and cortex [54,56]. Here, APP is linked to Alzheimer disease.