MAPT and Alzheimer disease: For example, previous studies using transgenic mouse models of AD have identified various mechanisms that lead to synaptic impairment in AD, including the accumulation of soluble amyloid-beta, Tau hyperphosphorylation, loss of VGF signaling, and glial state dysregulation (e.g., the induction of disease-associated microglia and disease-associated astrocytes) (9, 23, , , , , , –30).