INS and type 2 diabetes mellitus: Among the favored mechanisms underlying this connection, T2D-induced brain Aβ accumulation [140], tau hyperphosphorylation [141], Aβ-induced loss of insulin sensitivity [142], T2D-associated oxidative stress and inflammation [134], subclinical blood–brain barrier (BBB) breakdown [143], and defective insulin signaling [144] have been proposed.