Figure 1.

The probable linkage between Aβ, insulin signaling, tau pathology, and microglia activation in AD. The constant production of Aβ needs to be eliminated by microglia through endocytosis and/or by the drainage of micro-vessels, as evidenced by the association of Aβ plaques with microglia and micro-vessels in AD brain. However, the overloading of Aβ leads to the impairment of insulin sensing in the brain–blood barrier and parenchyma, which triggers the phosphorylation of tau and subsequently perturbs mitochondria and insulin secretion. The tau pathology could be propagated via the synapse and exosome in a microglia-dependent manner, eventually leading to neural atrophy.