FIGURE 2.

Mechanisms of senescent astrocytes in the pathologies of AD. (a) SASP factors produced by senescent astrocytes induce Aβ generation and tau hyperphosphorylation, contributing to Aβ deposition and NFTs formation. Neurons release glutamate, which cannot be cleared from the synapse by senescent astrocytes, leading to an accumulation of extracellular excitotoxic glutamate. The reduced secretion of neurotrophic growth factors (NGF, IGF-1) in senescent astrocytes may lead to decreased neuronal growth or increased neuronal loss. (b) Senescent astrocytes secrete IFNγ and IL-6, which activate microglia and limit Aβ uptake by microglia. (c) SASP factors also disrupt endothelial tight junctions and induce leukocyte transmigration, resulting in BBB disruption.