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Insulin resistance, oxidative stress, and Aβ pathology. Downregulation of Akt and perturbation of the activities of the IDE lead to aggregation of amyloid-beta plaques and hyperphosphorylation of tau protein. On the other hand, chronic hyperglycemia directly promotes oxidative stress and neuroinflammation and causes neurodegeneration. Aβ = amyloid-beta; IDE = insulin-degrading enzyme; GSK3β = glycogen synthase kinase 3 beta.
