In AD, neurons could release soluble neurotoxic Aβ peptides to the extracellular space, which in turn stimulate microglial cells to produce proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-a) and reactive oxygen species (ROS), leading to the activation of astrocytes around the area of the extracellular beta-amyloid plaques [50,51,52]. Here, TNF is linked to Alzheimer disease.